It is an inherited cystic disease of the kidney. There are two types:

1. Adult PKD (APKD): It is inherited as autosomal dominant, common type, males and females are equally affected. Gene on chromosome 16 (PKD1) and 4 (PKD2).
2. Infantile PKD (IPKD): It is inherited as autosomal recessive, rare, associated with cyst in other organs and hepatic fibrosis and fatal in first year due to hepatic or renal failure. Gene on chromosome 6.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Simple cyst, usually congenital
• Acquired cyst, after dialysis (in chronic renal failure)
• Polycystic kidney disease
• Medullary sponge kidney: Cause is unknown, but not genetic. Cyst is confined to the papillary collecting ducts. Age 40 to 60 years, prognosis is good. Usually no hypertension or no renal failure.
• Medullary cystic disease: Small cysts in cortical area or corticomedullary junction. Renal failure is common, hypertension may occur. The patients usually have polyuria and increased thirst and are salt loser.

*Long Cases in Clinical Medicine, ABM Abdullah

Note: Remember the following points:

• Polycystic kidney disease is always bilateral (may be unilateral, if other kidney is absent)
• Polycystic kidney disease is a misnomer, cyst occurs in many other organs (liver, spleen)
• More common in sickle cell disease, cystic fibrosis, Huntington’s disease
• May be associated with mitral valve prolapse (25%), causing mitral regurgitation, and aortic
  regurgitation (rarely severe)
• Colonic diverticula may occur
• Abdominal wall hernia
• Polycystic kidney disease is not premalignant
• Hypertension is present in 75% cases
• Usually there is polycythemia due to high erythropoietin level. There may be anemia if there is chronic renal failure (however, hemoglobin level is higher than expected for the degree of renal failure).

*Long Cases in Clinical Medicine, ABM Abdullah

Mode of inheritance are:

• Adult polycystic kidney disease—Autosomal dominant
• Infantile polycystic kidney disease—Autosomal recessive.

Pain is due to:

• Acute hemorrhage in the cyst
• Infection in the cyst
• Renal stone
• Renal cell carcinoma rarely.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• May be asymptomatic (renal mass detected on routine examination)
• Vague discomfort, pain or heaviness in loin or abdomen due to increasing mass of renal tissue.
• Recurrent painful hematuria (due to rupture of cyst in renal pelvis or infection) (with little or no proteinuria)
• Recurrent UTI or cyst infection
• Acute loin pain or renal colic due to hemorrhage into a cyst
• Features of hypertension (usually after 20 years of age) and its complications
• Features of renal failure
• CVA (usually subarachnoid hemorrhage, due to rupture of berry aneurysm. Sometimes, may be cerebral hemorrhage as a complication of hypertension).

*Long Cases in Clinical Medicine, ABM Abdullah; Pre-exam preparation for medicine, HN Sarker

As follows:

• Cystic liver—30%, but hepatic dysfunction is rare. There may be cyst in spleen, ovary and pancreas
• Berry aneurysm in circle of Willis—10% (may rupture causing subarachnoid hemorrhage)
• Polycythemia (due to increased erythropoietin secretion)
• Renal stone—10% cases (usually calcium oxalate, urate)
• Renal neoplasm—rarely.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Ultrasonography (always mention as the first investigation)
• Urine for R/E and C/S
• Full blood count (polycythemia may be found)
• Renal functions—urea, creatinine, serum electrolytes (some patients may be salt looser)
• High resolution CT-Scan or MRI of KUB
• IVU or retrograde pyelography
• Family screening.

*Long Cases in Clinical Medicine, ABM Abdullah

Figure: MRI images of the kidneys. A Normal kidneys. B Polycystic kidneys; although the kidney enlargement is extreme, this patient had only slightly reduced GFR.

Figure: Davidson’s Principles and Practice of Medicine, 22nd edition

Ultra sonogram of whole abdomen.

USG criteria are:

• Person below 30 years—presence of at least 2 renal cysts (unilateral/bilateral)
• Person between 30 to 59 years—presence of at least 2 renal cysts in each kidney
• Persons 60 years and above—at least 4 cyst in each kidney.

*Long Cases in Clinical Medicine, ABM Abdullah

IVU shows:

• Enlargement of both the kidneys
• Stretching, distortion and elongation of pelvicalyceal system (giving rise to spidery appearance).

*Long Cases in Clinical Medicine, ABM Abdullah

Bilateral hydronephrosis with hypertension.

*Long Cases in Clinical Medicine, ABM Abdullah

Subarachnoid hemorrhage due to rupture of berry aneurysm.

Other causes may be:

• Cerebral hemorrhage as a complication of hypertension
• Hyponatremia (salt losing nephropathy).

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Control of hypertension
• Control of urinary tract infection
• Plenty of fluid
• Salt (there may be salt looser in some cases)
• For renal pain or if large cyst, ultrasonic guided aspiration or laparoscopic cystectomy may be
  done
• Treatment of renal failure. Dialysis and even renal transplantation may be done
• Genetic counseling
• Family screening—USG of the abdomen should be done in all members of the family over 20
  years of age to detect cysts.
• MR angiography to detect berry aneurysm may be considered in some cases, where other members
  having history of subarachnoid hemorrhage.

*Long Cases in Clinical Medicine, ABM Abdullah

Death may be due to:

• Chronic renal failure (in one third cases)
• Intracerebral hemorrhage (SAH)
• Myocardial infarction.

*Long Cases in Clinical Medicine, ABM Abdullah

Chronic kidney disease (CKD), previously termed chronic renal failure, refers to an irreversible deterioration in renal function which usually develops over a period of years.

* Davidson’s Principles and practice of medicine, 22nd edition

Chronic kidney disease is defined as structural or functional abnormalities of kidney present for >3 months, which is usually irreversible.

* Lecture, Assoc. Prof. Dr Swapan Kumar Mondal

End stage renal disease or failure (ESRD) is a stage when renal replacement therapy is compulsory either dialysis or renal transplantation, without which death is likely.

*Long Cases in Clinical Medicine, ABM Abdullah

This is a group of metabolic bone disease secondary to chronic renal failure. It comprises the following:

• Osteomalacia (or ricket, called renal ricket)
• Osteoporosis
• Osteosclerosis (in vertebral body, giving rise to Rugger jersey spine)
• Osteitis fibrosa cystica (Hyperparathyroid bone disease)

Note: Remember the following:
There may be adynamic bone disease in which bone formation and resorption are both depressed. Cause is unknown, may cause spontaneous fracture. There may be hypercalcemia, normal alkaline phosphatase, PTH is low, dual X-ray absorptiometry shows osteopenia. No proven treatment.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

Renal replacement therapy means the facility to replace functions of the kidney.

*Short and Long Cases in Clinical Medicine, HN Sarker

Types of renal replacement therapy are:

1. Hemodialysis— Removal of toxic elements from the blood, which is filtered through a membrane while circulated outside of the body through a machine.
2. Hemofiltration.
3. Peritoneal dialysis—Filtration through the lining membrane of the abdominal cavity; fluid is instilled into the peritoneal cavity, then drained.
4. Renal transplantation.

Figure: Options for renal replacement therapy. A In haemodialysis, there is diffusion of solutes from blood to dialysate across a semipermeable membrane down a concentration gradient. B In haemofiltration, both water and solutes are filtered across a porous semipermeable membrane by a pressure gradient. Replacement fluid is added to the filtered blood before it is returned to the patient. C In peritoneal dialysis (PD), fluid is introduced into the abdominal cavity using a catheter. Solutes diffuse from blood across the peritoneal membrane to PD fluid down a concentration gradient and water diffuses through osmosis (see text for details). D In transplantation, the blood supply of the transplanted kidney is anastomosed to the internal iliac vessels and the ureter to the bladder. The transplanted kidney replaces all functions of the failed kidney.

*Pre-exam preparation for medicine, HN Sarker; Figure: Davidson’s Principles and practice of medicine, 22nd edition

Dialysis is a process for removing waste materials and excess water from the blood, and is used primarily as an artificial replacement for lost kidney function in people with renal failure.

*Short and Long Cases in Clinical Medicine, HN Sarker

1. Peritoneal dialysis
2. Hemodialysis

As follows:

1. Glomerular diseases (30 to 40%), e.g. IgA nephropathy (most common**), MCGN
2. Diabetes mellitus (20 to 40%)
3. Hypertension (5 to 20%)
4. Obstructive uropathy (reflux nephropathy)
5. Chronic pyelonephritis (infective cause)
6. Tubulointerstitial diseases (5 to 10%) (Often drug induced ** – analgesic nephropathy)
7. Systemic inflammatory diseases (5 to 10%), e.g. SLE, vasculitis
8. Renal artery stenosis (5%)
9. Congenital and inherited (5%), e.g. polycystic kidney disease, Alport’s syndrome
10. Unknown (5 to 20%).

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker; Lecture, Assoc. Prof. Dr Swapan Kumar Mondal; ** Davidson’s Principles and practice of medicine, 22nd edition; 

Chronic glomerulonephritis is the most common cause of CRF in developing countries.

*Short and Long Cases in Clinical Medicine, HN Sarker

Common causes of CKD worldwide are:
– Diabetes mellitus
– Hypertension
– Chronic glomerulonephritis.

*Short and Long Cases in Clinical Medicine, HN Sarker

Inherited causes of chronic kidney disease are:
– Polycystic kidney disease
– Alport’s syndrome.

*Pre-exam preparation for medicine, HN Sarker

As follows:

• Hypertension
• Reduced renal perfusion, such as—renal artery stenosis, hypotension due to drug treatment, sodium and water depletion, poor cardiac function
• Urinary tract infection
• Urinary tract obstruction
• Other systemic infections that causes increased catabolism and urea production
• Nephrotoxic drugs.

*Long Cases in Clinical Medicine, ABM Abdullah

CKD stage-1	GFR ≥9o ml/min/1.73 m­2 but other evidence of kidney disease	Kidney damage with normal or ↑ GFR
CKD stage-2	GFR 60-89 ml/min/1.73 m­2, with other evidence of kidney damage	Kidney damage with mild ↓ GFR
CKD stage-3	GFR 30-59 ml/min/1.73 m­2, with or without other evidence of kidney disease	Moderate ↓ GFR A and B (A: 45-59, B: 30-44)**
CKD stage-4	GFR 15-29 ml/min/1.73 m­2	Severe ↓ GFR
CKD stage-5	GFR 2 or patient is on dialysis	Kidney failure

*Lecture, Assoc. Prof. Dr Swapan Kumar Mondal; Pre-exam preparation for medicine, HN Sarker; **Long Cases in Clinical Medicine, ABM Abdullah.

Anemia is common in CKD, correlates with the severity of renal failure. It is usually normocytic and normochromic. The mechanisms are:

• Relative deficiency of  erythropoietin*** (most significant)
• Diminished erythropoiesis due to toxic effects of uremia on bone marrow precursor cells. (Also by PTH, ACE inhibitor*)
• Reduced dietary intake and absorption and utilization of iron.** (Reduced dietary intake and absorption of hematinics – iron, vitamin B12, folic acid.**)
• Reduced red cell survival (Increased red cell destruction may also be during hemodialysis due to mechanical, oxidant and thermal damage*)
• Increased blood loss due to capillary fragility, poor platelet function**, occult gastrointestinal bleeding and blood loss during hemodialysis*
• Erythropoietin alpha therapy may cause anemia (by pure red cell aplasia).*

Note Remember the following:

– Anemia is less severe or absent in polycystic kidney disease, as erythropoietin is relatively more in this case.
– In CKD, the patient can tolerate mild to moderate anemia, because there is more release of oxygen from hemoglobin. The mechanisms are—in CKD patient, there is acidosis and high 2, 3 DPG level in RBC, which shifts the oxygen dissociation curve to the right and more oxygen is released from hemoglobin. So, the patient doesn’t require blood transfusion in mild to moderate anemia. Target hemoglobin is 11 to 12.5 g/dL.
– Anemia becomes obvious in stage B CKD.
– ***Relative deficiency of erythropoietin production: Until recently, it was believed that this was due to progressive destruction of erythropoietin producing cells in the kidney, leading to a reduced cellular capacity for erythropoietin production. More recent work, involving pharmacological inhibition of prolyl hydroxylase, suggests that there may be a defect of the oxygen-sensing system, rendering functioning cells less sensitive to hypoxia.

*Long Cases in Clinical Medicine, ABM Abdullah; ** Davidson’s Principles and Practice of Medicine, 22nd edition; Short and Long Cases in Clinical Medicine, HN Sarker; *** Oxford Textbook of Clinical Nephrology, 4th edition

As follows:

• Osteomalacia is secondary to deficiency of 1, 25-dihydroxycholecalciferol as kidney is unable to convert 25 hydroxycholecalciferol to 1,25 dihydroxycholecalciferol, due to deficiency of 1 α-hydroxylase enzyme
• Osteoporosis, though its mechanism is unknown, may be due to secondary hyperparathyroidism and hypocalcemia, also probably due to malnutrition
• Osteosclerosis—due to hyperparathyroidism which causes increased bone density, particularly seen in the spine in which there is bands of sclerosis in the margin and porotic bone in between, giving rise to Rugger jersey spine
• Osteitis fibrosa cystica—due to secondary hyperparathyroidism.

 Figure: Rugger jersey spine.

*Long Cases in Clinical Medicine, ABM Abdullah

The common renal diseases causing hypertension are:
– Glomerulonephritis
– Renovascular disease
– Interstitial diseases
– Renal artery stenosis
– Polycystic kidney disease.

*Pre-exam preparation for medicine, HN Sarker

CKD refers to all stages ranging from kidney damage with normal or raised GFR to kidney failure but CRF means at least some impairment of renal function.

*Short and Long Cases in Clinical Medicine, HN Sarker

As follows:

1. May be asymptomatic, until GFR falls below 30 mL/min/1.73 m­² of body surface area. Detected on routine blood biochemistry. High urea and creatinine may be found on routine investigation, sometimes there may be hypertension, anemia, proteinuria on routine urine examination.
2. General features—early features may be (when GFR falls bellow 15-20 ml/min/1.73 m­² symptoms and signs are common) –
   • nocturia (due to loss of concentration ability), polyuria,
   • anorexia, nausea, vomiting, diarrhea,
   • weakness, malaise, insomnia,
   • breathlessness on exertion,
   • paresthesia, bone pain, edema,
   • amenorrhea in woman, sexual dysfunction in man.
3. In ESRF—general features are more severe, and CNS symptoms may be more. Features like –
   • hiccup, pruritus,
   • deep respiration (Kussmaul’s respiration), muscular twitching,
   • fit, drowsiness, even coma may occur.
4. Other features may be present, which may occur due to involvement of different systems of the body.

*Long Cases in Clinical Medicine, ABM Abdullah; Pre-exam preparation for medicine, HN Sarker; Lecture, Assoc. Prof. Dr Swapan Kumar Mondal

Stigmata of chronic kidney disease are:

1. Pallor
2. Pruritus
3. Pigmentation
4. Persistent hypertension
5. Progressive back pain (renal osteodystrophy)
6. Proximal myopathy
7. Peripheral neuropathy.

*Pre-exam preparation for medicine, HN Sarker

CKD can involve any system of the body, symptoms and signs may develop according to the involvement:

1. Bone diseases (renal osteodystrophy):
   • Osteomalacia (or ricket called renal ricket)
   • Osteoporosis
   • Osteosclerosis (in vertebral body, giving rise to Rugger Jersey spine)
   • Osteitis fibrosa cystica.
2. Skin disease:
   • Pruritus—due to retention of nitrogenous waste products, hypercalcemia, hyperphosphatemia, hyperparathyroidism and iron deficiency. Patient on dialysis, inadequate dialysis may have pruritus due to unknown mechanism
   • Dry skin
   • Eczematous lesions, particularly near arteriovenous fistula
   • Ecchymosis in advanced disease due to increased bleeding tendency
   • Porphyria cutanea tarda (PCT) due to decreased hepatic uroporphyrinogen decarboxylase and decreased clearance of porphyrins in urine or by dialysis
   • Pseudoporphyria (features like PCT but without enzyme deficiency).
3. Gastrointestinal—anorexia, nausea, vomiting. Also there may be decreased gastric emptying, increased risk of reflux esophagitis, peptic ulceration, acute pancreatitis and constipation.
4. Metabolic abnormalities:
   • Hyponatremia, hyperkalemia or sometimes hypokalemia
   • Metabolic acidosis (due to increased tissue catabolism and retention of organic acids)
   • Hyperuricemia and gout
   • Hypocalcemia, hyperphosphatemia
   • Lipid abnormalities (hypercholesterolemia, hypertriglyceridemia).
5. Endocrine abnormalities:
   • Secondary hyperparathyroidism, may be tertiary
   • Prolonged half-life of insulin, due to reduced tubular metabolism of insulin. Also, insulin requirement in a diabetic patient decreases. But in advanced CKD, there may be end organ resistance to insulin, leading to impaired glucose tolerance
   • Hyperprolactinemia (presents with galactorrhea in men as well as women, loss of libido and sexual dysfunction in both sexes).
   • Others—increased LH, decreased serum testosterone (erectile dysfunction, decreased spermatogenesis), oligomenorrhea or amenorrhea (in female), impaired growth in children, abnormal thyroid hormone levels (hypothyroid feature), partly because of altered protein binding.
6. Muscle dysfunction:
   • Generalized myopathy (due to the combination of poor nutrition, vitamin D deficiency, electrolyte abnormalities, hyperparathyroidism)
   • Muscle cramps
   • Restless leg syndrome.
7. Nervous system:
   • Peripheral nervous system:
     1. Polyneuropathy—both motor and sensory. Improves or resolve with dialysis
     2. Median nerve compression in the carpal tunnel due to β 2 microglobulin related amyloidosis
     3. Restless leg syndrome.
   • Central nervous system:
     1. Clouding of consciousness, convulsion, coma
     2. Asterixis (flapping tremor)
     3. Tremor
     4. Myoclonus
     5. Dialysis disequlibrium syndrome
     6. Dialysis dementia
     7. Psychiatric problems—(anxiety, depression, phobia, psychosis)
     8. CVD secondary to hypertension.
   • Autonomic dysfunction:
     1. Postural hypotension
     2. Fixed heart rate
     3. Urinary retention or incontinence
     4. Constipation
     5. Impotence
     6. Pupillary constriction
     7. Gustatory sweating
     8. Anhydrosis.
8. Calciphylaxis (calcific uremic arteriolopathy)—rare but life threatening
9. Cardiovascular:
   • Hypertension
   • Cardiac failure
   • Pericarditis, pericardial effusion or tamponade, chronic constrictive pericarditis
   • Uremic cardiomyopathy
   • Increased atherosclerosis
   • Left ventricular hypertrophy is common in ESRF, even arrhythmia leading to death may occur
   • Systolic dysfunction due to myocardial fibrosis, abnormal myocyte function due to uremia, calcium overload and hyperparathyroidism, carnitine and selenium deficiency
   • Coronary artery calcification.
10. Respiratory—pulmonary edema (uremic lung) due to fluid overload
11. Malignancy—incidence is increased in CKD (RCC)
12. Nephrogenic systemic fibrosis—seen in patients with moderate to severe CKD, particularly those on dialysis. There is skin involvement with plaques, papules and nodules. The affected skin becomes thick, firm and assume a peau d’orange appearance. There is also muscle stiffness, joint contracture and fibrosis of lungs, pleura, diaphragm, myocardium, pericardium and dura mater. Probably Gadolinium containing contrast agent is responsible for this.

 

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

1. Urine:
   • Urine R/M/E (to see pus cell, RBC or WBC cast, glycosuria, proteinuria, specific gravity) and culture
   • 24 hour urinary protein
   • Creatinine clearance
2. Blood
   • CBC with PBF (shows normocytic, normochromic anemia), ↑ESR
   • Renal function tests (blood urea and serum creatinine are elevated)
   • Serum electrolytes (hyperkalemia, acidosis)
   • Serum calcium, phosphate, PTH: ↓Ca⁺⁺,↑PO₄ ,↑PTH
   • Serum uric acid (may be high)
   • Serum albumin: Low
   • Serum immunoelectrophoresis
   • Blood glucose: If diabetes mellitus
   • Serum iron profile: If anemia
   • Lipid profile: Cardiovascular risk
3. Imaging
   • USG of the whole abdomen (shows shrunken kidneys. Kidneys may be large in diabetic glomerulosclerosis, amyloidosis, PKD and bilateral hydronephrosis)
   • Plain X-ray KUB (calcification, renal stone, kidney size may be seen)
   • Chest X-ray: Pulmonary edema, cardiomegaly
   • CT scan of abdomen
   • Pyelogram (intravenous or retrograde) (rarely needed)
   • Isotope renogram
   • Renal artery Doppler study
   • Renal angiography and DTPA scan
4. Renal biopsy (may be needed in some cases)
5. ECG: Ischemic disease
6. Other investigation according to suspicion of cause (autoantibody screening, ANA and anti ds-DNA for SLE, complement components, screening for hepatitis B and C, HIV, and immune complexes.).

Sugegsted reading: Urinalysis (investigations and normal findings) – WebMed, Aarogya

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition; Lecture, Assoc. Prof. Dr Swapan Kumar Mondal

Renal ultrasound—

1. Bilateral small kidney, cortical echogenicity increaded, poor corticomedullary differentiation are usual finding in advanced renal failure. Small kidneys suggest chronicity.
2. Structural abnormalities, such as polycystic kidneys, also may be observed.
   • This is a useful test to screen for hydronephrosis.
   • Asymmetric renal size suggests renovascular or developmental disease.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition; Lecture, Assoc. Prof. Dr Swapan Kumar Mondal

1. Diabetic nephropathy (early)
2. Polycystic kidney disease
3. Obstructive uropathy
4. Infiltrative disease, e.g. amyloidosis, lymphoma
5. Acute renal vein thrombosis

*Short and Long Cases in Clinical Medicine, HN Sarker

A 54-year-old male presents with anorexia, nausea, nocturia, and recurrent swelling of face and feet for 6 months. Swelling is more in face and in the morning without any breathlessness, renal and cardiac disease but has an elevated level of serum creatinine. On examination, he is pale and has anemia, periorbital puffiness, half and half nail, scratch marks, mild- pitting edema, and BP 160/95 mm Hg. Bedside urine examination reveals presence of 2+ proteinuria. So, I consider this diagnosis.

*Short and Long Cases in Clinical Medicine, HN Sarker

As swelling is more in face and in the morning without any breathlessness, chest pain and history of cardiac disease but has an elevated level of serum creatinine. On examination, he is pale and has anemia, periorbital puffiness, half and half nail, scratch marks, mild pitting edema, and BP 160/95 mm Hg but JVP is not raised and liver is not enlarged and tender.

*Short and Long Cases in Clinical Medicine, HN Sarker

History of 6 months’ illness, S. creatinine 2. 9 mg/dL 4 month back, presence of anemia, half and half nail, scratch marks, and elevated blood pressure exclude acute renal failure.

*Short and Long Cases in Clinical Medicine, HN Sarker

History of more than 3 months, polyuria, nocturia, anemia, pruritus, long standing hypertension, renal osteodystrophy, peripheral neuropathy and myopathy favour the diagnosis of chronic renal failure.

*Short and Long Cases in Clinical Medicine, HN Sarker

1. Dietary and lifestyle interventions:
   • Protein (0.8-1.2 gm/kg/day)
   • Salt (<5 gm/day)
   • Fluid: According to urine output
   • Fruit and juice restriction
   • All patients should be advised to stop smoking, since there is evidence that this slows the decline in renal function in addition to reducing cardiovascular risk.
   • Exercise and weight loss may also reduce proteinuria and have beneficial effects on cardiovascular risk profile.
2. Control of hypertension (Goal – BP <120/80 mm Hg)
   • Calcium channel blockers, β-blockers
   • α-blockers
   • Diuretics
3. Control of proteinuria: ACE-I/ARB (Goal – proteinuria < 0.3 g/24 hours)
4. Control of diabetes mellitus
5. Treatment of dyslipidemia
6. Treatment of complications
   • Fluid overload: Diuretics
   • Hyperkalemia: Diuretics, nebulization, Ca⁺⁺ gluconate
   • Metabolic acidosis: Sodibicarb
   • Renal osteodystrophy: Vit. D, calcium carbonate
   • Anemia: Iron, erythropoietin
7. Renal replacement therapy (RRT)
   • Hemodialysis
   • Peritoneal dialysis
   • Kidney transplantation

* Lecture, Assoc. Prof. Dr Swapan Kumar Mondal; Davidson’s Principles and Practice of Medicine, 22nd edition

 

• First look for iron deficiency – correct by iron supplementation.
• Then, recombinant human erythropoietin (EPO) – target Hb level 10-12 g/dL. Side effects are hypertension and thrombosis (including thrombosis of arteriovenous fistula, used for hemodialysis). Erythropoietin is less effective in the presence of iron deficiency, active inflammation or malignancy, and in patients with aluminium overload, which may occur in dialysis.
• Blood transfusion may be given in severe anemia. Risk of blood transfusion in CKD patient—fluid overload, potassium overload, increased chance of graft rejection after kidney transplant, so blood transfusion is better to be avoided. In severe anemia, BT should be given during hemodyalisis.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition

 

Treatment modalities are:

1. Pharmacological—
   • 10% glucose and insulin
   • Salbutamol nebulization
2. Dialysis
3. Dietary potassium restriction.

*Short and Long Cases in Clinical Medicine, HN Sarker

The drugs are tetracycline, frusemide and cephalosporin, aminoglycosides, potassium salt and potassium sparing diuretics.

*Short and Long Cases in Clinical Medicine, HN Sarker

ACE inhibitor and angiotensin II receptor antagonists are the drugs of choice because of their antihypertensive and antiproteinuric effects.

*Short and Long Cases in Clinical Medicine, HN Sarker

In CKD glomerular perfusion is maintained by increased glomerular pressure caused by angiotensin II mediated vesoconstriction of the efferent arteriole; though it is immediately benificial but ultimately destructive as increased glomerular pressure predisposes to glomerular sclerosis.

*Short and Long Cases in Clinical Medicine, HN Sarker

ACE inhibitor or ARBs should not be given in –

• Hyperkalaemia
• Bilateral renal artery stenosis
• When serum creatinine is 5 mg/dL or more.

*Short and Long Cases in Clinical Medicine, HN Sarker

After initiation of these drug, serum creatinine may rise up to by 30% but if it remains constant and serum potassium is within normal limit, drug should be continued with frequent monitoring.

*Short and Long Cases in Clinical Medicine, HN Sarker

As follows:

• Treatment of renal failure
• Calcium supplement
• 1-α hydroxylated synthetic analog of vitamin D (active vitamin D).

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Severe hyperkalemia
• Pulmonary edema or severe fluid overload
• Severe metabolic acidosis
• Uremic pericarditis
• Uremic encephalopathy
• Toxicity with a dialyzable poison (methanol, barbiturate, etc.)
• Recurrent vomiting due to uremia.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Hyperkalemia (plasma potassium > 6 mmol/L) if not corrected by medical treatment
• Metabolic acidosis if medical treatment fails (H⁺ > 56 nmol/L, pH < 7.25), HCO₃ < 10 mmol/L
• Fluid overload and pulmonary edema if not responding to diuretic therapy
• Serum creatinine > 600 μmol/L, or e.GFR < 8
• Plasma urea level is >30 mmol/L
• Uremic pericarditis or encephalopathy

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

As follows:

1. Absolute:
   • Active malignancy – a period of at least 2 years of complete remission recommended for most tumors
   • Active vasculitis or recent anti GBM disease
   • Severe heart disease or any severe co-morbid condition
   • Severe occlusive aorto-iliac vascular disease.
2. Relative:
   • Age—while practice varies, transplants are not routinely offered to very young children (< 1 year) or older people (>75 years)
   • High risk of disease recurrence in the transplant kidney
   • Disease of the lower urinary tract—in patients with impaired bladder function, stricture urethra (ileal conduit may be considered.)
   • Significant co-morbidity.

*Long Cases in Clinical Medicine, ABM Abdullah

Usually a combination of:

• Cyclosporine or tacrolimus
• Azathioprine or mycophenolate mofetil/ sirulimus or evanolimus
• Prednisolone.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Acute rejection
• Chronic rejection
• Infection—CMV, pneumocystis jiroveci, oral candidiasis, polioma virus. Bacterial infection is common in first few months
• Complication of immunosuppressive drugs including steroid
• Acute tubular necrosis (ATN)—it is the most common cause of cadaveric graft dysfunction (40 to 50%). It is associated with a worse long-term outcome and predisposes to rejection.
• Technical failures—occlusion or stenosis of the arterial anastomosis, occlusion of the venous anastomosis and urinary leaks
• Post transplantation lymphoproliferative disorder—EBV associated malignancies (such as lymphoma) are common in patients who received biological agents and in children
• Chronic allograft nephropathy—most common cause of late graft failure
• Malignancy—skin tumor (including basal and squamous cell carcinoma), renal, cervical and vaginal
• Hypertension
• Atherosclerosis
• Recurrence of renal disease.

Complication of Renal transplantation (Remember the formula— ‘TROPICAL’): T–Thrombosis of graft kidney artery and vein R–Rejection of graft kidney O–Obstruction of graft ureter with perinephric hematoma, seroma, urinoma, or lymphocele P–Primary disease recurrence. The most common recurrence is MCGN type II (80 to 100%) I–Infection which may be bacterial (any, TB), Viral (CMV, chicken pox, polioma virus), fungal, (Cryptococcuus neoformans), Parasite (Pneumocystis jiroveci, ispspora cycloporium , microspora, Giardia) C–ciclosporine toxicity and other imunosupressive drugs toxicities A–Acute tubular necrosis L–Leakage of graft ureter due to error or ischemia.

*Long Cases in Clinical Medicine, ABM Abdullah

Acute rejection characterized by rising of creatinine, fever, loin pain, hypertension, swelling of the graft. Urine shows protein, lymphocyte, and renal tubular cells. Occurs in 10 to 30% cases within 6 months. Graft biopsy shows immune cell infiltrate and tubular damage.

Treatment—high dose methylprednisolone, resistant cases may require antithymocyte globulin or ALG or OKT3 may be used.

*Long Cases in Clinical Medicine, ABM Abdullah

It occurs usually after 6 months. The patient presents with gradual rise of creatinine and proteinuria. Graft biopsy shows vascular change, fibrosis and tubular atrophy. It is not responsive to increased immunosuppression.

*Long Cases in Clinical Medicine, ABM Abdullah

• Hypotension during dialysis due to fluid removal and hypovolemia. There may be chest pain and leg cramps
• Cardiac arrhythmia due to potassium and acid base shift
• Hemorrhage due to anticoagulation. Also, venous needle disconnection may lead to hemorrhage
• Anaphylactic reaction – dialyser hypersensitivity
• Between treatment – Pulmonary edema due to fluid overload, systemic sepsis usually involving vascular access devices
• Hemolytic reactions
• Air embolism
• Hard water syndrome
• Dialysis disequilibrium due to rapid correction of uremia.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

• CCF with low EF%
• Generalized atherosclerosis with poor vascular access for AVF. (They are the ideal candidate for peritoneal dialysis).

*Long Cases in Clinical Medicine, ABM Abdullah

• Peritonitis
• Catheter exit site infection
• Constipation
• Massive pleural effusion (dialysate leak through a diaphragmatic defect into the thoracic cavity). Dialysate may leak into the scrotum down through a patent processus vaginalis
• Ultrafiltration failure
• Failure of peritoneal membrane function due to long-term CAPD
• Sclerosing peritonitis (potentially fatal).

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

• Previous peritonitis causing peritoneal adhesions
• Presence of a stoma (e.g. colostomy)
• Active intra-abdominal sepsis (absolute contraindication)
• Abdominal hernia
• Co-morbidities like coronary artery disease, congestive cardiac failure..

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Cardiovascular disease
• Sepsis (leading cause of death in long term dialysis patient)
• Dialysis associated ascites
• Dialysis amyloidosis
• Dialysis associated arthropathy.

*Long Cases in Clinical Medicine, ABM Abdullah

Acute renal failure (ARF; also referred to as acute kidney injury, or AKI) describes a sudden and usually reversible loss of renal function, which develops over days or weeks and is usually accompanied by a reduction in urine volume.

*Pre-exam preparation for medicine, HN Sarker; Davidson’s Principles and Practice of Medicine, 22nd edition

Sudden deterioration in renal function, occurring within weeks or months (<3 months), biochemically detected by high urea and creatinine level. This is usually reversible.

*Long Cases in Clinical Medicine, ABM Abdullah

Grade	GFR criteria	UO criteria
Risk	SCr × 1. 5 UO	< 0. 5 mL/kg/hours × 6 hours
Injury	SCr × 2 UO	< 0. 5 mL/kg/hours × 12 hours
Failure	SCr × 3 or SCr > 350 μmol/L with an acute rise > 40 μmol/L	< 0. 3 mL/kg/hours × 24 hours UO < 0. 3 mL/kg/ hours × 24 hours
Loss	Persistent ARF > 4 weeks
ESKD	Persistent renal failure > 3 months

*Pre-exam preparation for medicine, HN Sarker

* Davidson’s Principles and Practice of Medicine, 22nd edition

Causes of ARF:

1. Prerenal: (Impaired perfusion)
   • Fluid loss due to diarrhea, vomiting, dehydration, etc
   • Blood loss due to hemorrhage.
   • Plasma loss in burn
   • Sepsis
   • Hypotension due to myocardial infarction, shock, vasodilator drugs, heart failure
   • Rhabdomyolysis
   • Hemolytic uremic syndrome
   • Hepatorenal syndrome
   • Renal artery occlusion or stenosis
   • Disease affecting arterioles.
     (Under perfusion to the kidney initially causes rapidly reversible changes. Subsequently, acute tubular necrosis or other changes cause long lasting but usually temporary intrinsic renal failure.)
2. Renal (intrinsic renal disease):
   • Glomerulonephritis e.g. MCGN, IgA nephropathy
   • Small-vessel vasculitis
   • Acute tubular necrosis
     • Drugs
     • Toxins
     • Prolonged hypotension
   • Interstitial nephritis
     • Drugs (NSAIDs, ciprofloxacin, allopurinol, sulfonamide, cyclosporine).
     • Toxins
     • Inflammatory disease such as SLE, rheumatoid arthritis, systemic sclerosis, multiple myeloma, vasculitis
     • Infection
3. Post renal:
   • Urethral— meatal stenosis/phimosis, paraphimosis, stricture/valves, stone, blood clot, slaughed papilla.
   • Bladder neck—benign prostatic enlargement, malginancy (prostate cancer, cervical cancer (?)), stone.
   • Bilateral ureteric—calculus, following surgery, pelvic tumor, uterine prolapse, retroperitoneal fibrosis (due to radiation, methysergide, idiopathic).

*Long Cases in Clinical Medicine, ABM Abdullah; Davidson’s Principles and Practice of Medicine, 22nd edition

This patient develops acute renal failure (ARF) due to
hypovolemia.

Correction of dehydration by appropriate fluid (e.g. cholera saline). Restoration of blood volume will restore kidney function and produce urine output.

If no urine output after rehydration, it indicates established ARF. So management of oliguric phase should be given—

• Hyperkalemia (a plasma K⁺ concentration > 6 mmol/L) must be treated immediately, to prevent life-threatening cardiac arrhythmias.
• Fluid—Daily fluid intake should equal to urine output plus an additional 500 mL to cover insensible losses.
• Protein and energy intake— In patients in whom dialysis is likely to be avoided, accumulation of urea is slowed by dietary protein restriction (to about 40 gm/day).
• Infection control.
• Drugs—Vasoactive drugs such as NSAIDs and ACE inhibitors and nephrotoxic drugs should be avoided.
• Renal replacement therapy.

*Short and Long Cases in Clinical Medicine, HN Sarker

Bacteriuria:

Bacteria in the urine is called bacteriuria. It may be asymptomatic or symptomatic.

* Oxford Handbook of Clinical Medicine, 9th Edition Page: 288

It is defined as >10⁵/mL organisms in urine of apparently healthy asymptomatic patients.

* Pre-exam preparation for medicine, HN Sarker

Urinary tract infection (UTI) is defined as multiplication of organisms in the urinary tract.

• It is usually associated with the presence of neutrophils and >10⁵ organisms/mL in midstream clean catch morning sample of urine (MSU).
• Exception in pregnancy >10⁴ organisms/mL as UTI has deleterious effects.

* Pre-exam preparation for medicine, HN Sarker; Oxford Handbook of Clinical Medicine, 9th Edition Page: 288

Upper UTI:

Upper urinary tract infection includes pyelonephritis (renal pelvis inflammation).

Lower UTI:

Lower urinary tract infection includes urethritis and cystitis (urethral and bladder inflammation respectively) (and prostatitis).

* Oxford Handbook of Clinical Medicine, 9th Edition Page: 288; Pre-exam preparation for medicine, HN Sarker

The infection to the pelvis and kidney is known as pyelitis or pyelonephritis.

* Pre-exam preparation for medicine, HN Sarker

Uncomplicated UTI means UTI occurring without any anatomical, physiological and immunological defect.

• Here, persistent or recurrent infection seldom results in serious kidney damage.

Complicated UTI means UTI occurring with anatomical (e.g.urethral stricture), physiological (e.g.vesicoureteric reflux) or immunological defect (e.g.diabetes).

• Here, persistent or recurrent infection results in serious kidney damage.

* Pre-exam preparation for medicine, HN Sarker

Relapse and reinfection are the types of recurrent infection.

* Pre-exam preparation for medicine, HN Sarker

Relapse is diagnosed by recurrence of bacteriuria with the same organism within 7 days of completion of antibacterial treatment and implies failure to eradicate infection.

Reinfection is when bacteriuria is absent after treatment for at least 14 days, usually longer, followed by recurrence of infection with the same or different organisms.

* Pre-exam preparation for medicine, HN Sarker

Strangury—Painful urge for micturition but unable to pass urine.

Dysuria—Painful micturition.

* Pre-exam preparation for medicine, HN Sarker

Typical organisms causing UTI in the community—

• E. coli (about 75% of infections)
• Proteus spp
• Pseudomonas spp
• Streptococci
• Staphylococcus epidermidis.

In hospital—

• E. coli
• Klebsiella
• Streptococci

* Pre-exam preparation for medicine, HN Sarker

Because of—

• The urethra is shorter
• Closer to perineum
• Absence of bactericidal prostatic secretions
• Sexual intercourse may cause minor urethral trauma and transfer bacteria from the perineum into the bladder.

* Pre-exam preparation for medicine, HN Sarker

Risk factors for urinary tract infection –

1. Incomplete bladder emptying
   • Bladder outflow obstruction
     • Benign prostatic enlargement
     • Prostate cancer
     • Urethral stricture
     • Vesico-ureteric reflux
   • Uterine prolapse
   • Neurological problems
     • Multiple sclerosis
     • Spina bifida
     • Diabetic neuropathy
2. Foreign bodies
   • Urethral catheter or ureteric stent
   • Urolithiasis
3. Loss of host defences
   • Atrophic urethritis and vaginitis in post-menopausal women
   • Diabetes mellitus

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 511

The spectrum of presentations are:

• Asymptomatic bacteriuria
• Symptomatic acute urethritis and cystitis
• Acute pyelonephritis
• Acute prostatitis
• Septicemia (usually Gram-negative bacteria).

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 511

Typical features of cystitis and urethritis (lower UTI) include:

• abrupt onset of frequency of micturition and urgency
• scalding pain in the urethra during micturition (dysuria)
• suprapubic pain during and after voiding
• intense desire to pass more urine after micturition, due to spasm of the inflamed bladder wall (strangury)
• urine that may appear cloudy and have an unpleasant odour
• microscopic or visible haematuria
• Systemic symptoms are usually slight or absent.

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 511

Ans. Common features of pyelonephritis are:

• Loin pain, guarding and tenderness
• Prominent systemic symptoms—Fever with rigors, vomiting and hypotension.

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 511

Investigation of patients with urinary tract infection:

1. All patients
   • Dipstick¹ estimation of nitrite, leucocyte esterase and glucose
   • Microscopy/cytometry of urine for white blood cells, organisms (MSU or urine obtained by suprapubic aspiration)
   • Urine culture
2. Infants, children, and anyone with fever or complicated infection
   • Full blood count; urea, electrolytes, creatinine
   • Blood cultures
3. Pyelonephritis; males; children; women with recurrent infections
   • Renal tract ultrasound or CT
   • Pelvic examination in women, rectal examination in men
4. Continuing haematuria or other suspicion of bladder lesion
   • Cystoscopy

¹May substitute for microscopy and culture in simple uncomplicated infection.

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 512

 

• A sterile test tube/container should be taken.
• Patient should be instructed to –
  • collect urine during first voiding after overnight sleep,
  • first part of urine flow is allowed to pass and
  • collect the middle part of the stream.

* Pre-exam preparation for medicine, HN Sarker

Criteria for diagnosis of bacteriuria are:

1. Symptomatic young women
   • ≥ 10² coliform organisms/mL urine plus pyuria (> 10 white blood cells/mm³) Or,
   •  ≥ 10⁵ any pathogenic organism/mL urine Or,
   • any growth of pathogenic organisms in urine by suprapubic aspiration
2. Symptomatic men
   • ≥ 10³ pathogenic organisms/mL urine
3. Asymptomatic patients
   • ≥ 10⁵ pathogenic organisms/mL urine on two occasion.

* Kumar and Clark’s Clinical Medicine, 9th Edition Box 20.23; Pre-exam preparation for medicine, HN Sarker

Treatment is started while awaiting urine C/S report

• Antibiotic:
  • Amoxicillin 250 mg 8-hourly
  • Nitrofurantoin 50 mg 6-hourly
  • Cephalexin 250 mg 6-hourly
  • Ciprofloxacin 100 mg 12-hourly
  • Co-amoxiclav 250/125 mg 8-hourly
• Duration:
  • 3 days in women
  • 10 days in men.

* Pre-exam preparation for medicine, HN Sarker

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 513

1. Counselling the parents about the disease
2. Antibiotics
   • Acute pyelonephritis
     • Ceftriazone IV 100 mg/kg/day or,
     • Cefotaxime IV 150 mg/kg/day or,
     • Gentamicin IV 5 mg/kg/day
     • Duration: 10–14 days.
   • Acute cystitis
     • Cotrimoxazol or
     • Amoxicillin or,
     • Co-amoxiclav or,
     • Cefadroxil or,
     • Ciprofloxacin
     • Duration: 5–7 days
3. Supportive treatment: More liquid intake, avoiding risk factors.

* Step on to Paediatrics, Md Abid Hossain Mollah, 3rd Edition Page: 220

Prophylactic measures to be adopted by women with recurrent urinary infections are:

• Fluid intake of at least 2 L/day
• Regular complete emptying of bladder
• Good personal hygiene
• Emptying of bladder before and after sexual intercourse
• Cranberry juice may be effective

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 513

• Antibiotic:
  • Co-amoxiclav 250/125mg 8-hourly
  • Amoxicillin 250 mg 8-hourly
  • Cephalexin 250 mg 6-hourly
• Duration: 7 days

Note:

Avoid trimethoprim and quinolones during pregnancy.

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 513

Treatment is usually needed in –

• infants,
• pregnant women and
• those with urinary tract abnormalities.

* Pre-exam preparation for medicine, HN Sarker

AGN is the inflammation in kidney characterized by hematuria, hypertension, edema (periorbital, leg or sacral) and oliguria. Urine shows proteinuria and red cell cast.

*Long Cases in Clinical Medicine, ABM Abdullah

Glomerulopathies present as nephritic syndrome are:
– Poststreptococcal glomerulonephritis
– Goodpasture’s disease (anti-GBM disease)
– IgA nephropathy
– Henoch-Schönlein purpura.

*Pre-exam preparation for medicine, HN Sarker

About 50%.

Causes are:

1. Infection—post-streptococcal commonest. Other infections include infective endocarditis, infectious mononucleosis, HBV, HCV, etc.
2. Non-infectious—SLE, Henoch-Schönlein purpura, cryoglobulinemia, etc.
3. Primary glomerular disease—diffuse proliferative GN, IgA nephropathy, membranous GN, focal segmental GN.
4. Shunt nephritis.

*Long Cases in Clinical Medicine, ABM Abdullah

Mechanisms of nephritic syndrome are:
– Inflammation
– Reactive cell proliferation
– Breaks in GBM
– Crescent formation.

*Pre-exam preparation for medicine, HN Sarker

No, antibody formed against streptococcal antigen cross react with glomerular protein due to molecular mimicry.

Immune-mediated.

Causes are:
– Focal segmental (necrotizing) glomerulonephritis
– SLE
– Goodpasture’s (anti-GBM ) disease
– IgA nephropathy.

*Pre-exam preparation for medicine, HN Sarker

As follows:

• Post-streptococcal glomerulonephritis (PSGN)
• Subacute bacterial infection: Especially infective endocarditis
• Mesangiocapillary glomerulonephritis, usually type II (90% in type II and 70% in type I)
• Cryoglobulinemia
• Lupus nephritis

*Long Cases in Clinical Medicine, ABM Abdul; Pre-exam preparation for medicine, HN Sarker

The latency is usually about 10 days after a throat infection or longer (2–3 weeks) after skin infection.

*Pre-exam preparation for medicine, HN Sarker

IgA nephropathy.

*Pre-exam preparation for medicine, HN Sarker

Features of nephritic syndrome are:
– Hematuria (red or brown urine)
– Edema and generalized fluid retention
– Hypertension
– Oliguria.

*Pre-exam preparation for medicine, HN Sarker

Symptoms—
– Swelling of the face followed by generalized swelling
– Scanty high colored urine (smoky)
– Sometimes history of sore throat/skin infections 2–3 weeks back.
Signs—
– Puffy face
– Pitting edema
– Hypertension
– Evidence of skin infection
– Signs of complications.

*Pre-exam preparation for medicine, HN Sarker

The mechanisms of hypertension in AGN are:

• Hypervolemia due to salt and water retention secondary to oliguria.
• Secondary hyperaldosteronism due to stimulation of renin angiotensin aldosterone axis.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

The mechanisms of edema formation in AGN are due to:

• Retension of salt and water
• Hypoproteinemia

*Short and Long Cases in Clinical Medicine, HN Sarker

• Presence of oligouria, hematuria and proteinuria (as in child)
• Edema is not marked.
• Hypertension may or may not be present
• There is no history of preceding infection

*Short and Long Cases in Clinical Medicine, HN Sarker

As follows:

1. Urine R/M/E:
   • Urine looks smoky.
   • It shows mild to moderate proteinuria, RBC, RBC cast and granular cast (RBC cast is suggestive of AGN)
2. 24 hours urinary total protein (increases, but less than 3 g/L) and volume is less
3. Renal function test
   • Blood urea, serum creatinine – may be raised
   • serum electrolytes – K⁺ may be raised
4. CBC (leukocytosis may be present)
5. Serum C3 and C4 level: Decreased
6. ASO titer (may be high in post-streptococcal glomerulonephritis)
7. Bacteriological
   • Throat swab for C/S to find streptococcal infection
   • Pus from skin lesion for C/S
8. USG of the whole abdomen (to look for renal pathology)
9. CXR (cardiomegaly or pulmonary edema if LVF)
10. Other investigation according to suspicion of causes:
    • ANA, Anti-dsDNA, C3, C4 (if the history is suggestive of SLE)
    • P-ANCA, c-ANCA (if the history is suggestive of vasculitis)
    • HbsAg, Anti-HCV
    • Renal biopsy may be done in some cases

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

Urine— R/M/E

• RBC ++
• Cast— RBC and granular cast
• Albumin +/++
• Dysmorphic RBC in phase contrast microscopy.

*Pre-exam preparation for medicine, HN Sarker

Presence of dysmorphic RBC under phase contrast microscopy and/or RBC cast in urine.

Casts are cylindrical structures (shape of renal tubule) composed mainly of mucoprotein (the Tamm-Horsefall mucoprotein) which is secreted by epithelial cells lining the loops of Henle, the distal tubules and the collecting ducts.
Common casts include—
Hyaline cast—Nephrotic syndrome
Granular cast—Urinary tract infection
RBC cast—Glomerulonephritis.

*Pre-exam preparation for medicine, HN Sarker

As follows:

• RBC cast—AGN
• WBC cast—Pyelonephritis
• Granular cast—GN
• Hyaline cast—Normal finding.

*Long Cases in Clinical Medicine, ABM Abdullah

Diagnosis is acute glomerulonephritis.

Poststreptococcal glomerulonephritis is the probable cause.

History of:
– Skin infection (infected scabies)
– Sore throat

• Nephrotic syndrome
• Angioneurotic edema

Because in nephrotic syndrome, there will be generalized edema, massive proteinuria which are absent in this case. (Serum protein will show hypoalbuminemia).

In this case, there is history of infected scabies, acute onset of facial puffiness followed by scanty smoky urine (oligouria and hematuria), absence of generalized edema, presence of hypertension. These are against NS.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker

IgA nephropaty usually follows respiratory tract infection and latent period is about 3 days.

Presence of hypertension, oligouria and hematuria, and absence of itchy swelling of eyelids, lips and tongue; no history of atopy – all these exclude angioneurotic edema.

*Short and Long Cases in Clinical Medicine, HN Sarker

Because there is no anorexia, nausea or vomiting. Also, previous history of sore throat followed by scanty micturition is in favor of AGN.

*Long Cases in Clinical Medicine, ABM Abdullah

Traits	AGN	Nephrotic syndrome
Age	5-15 years usually* 5-12 years**	2-6 years usually* 2-8 years**
History: Pharyngitis or skin infection	Present	Absent
Clinical features: Hematuria Oligouria Scratch mark Hypertension	Present Present May be present Present	Absent Absent Absent May be present
Urine examination Color Protein RBC and RBC cast Granular cast	High color Mild to moderate Present Absent	Normal Massive Absent Present
Serum Albumin Cholesterol C3 level	Normal Normal Low	Decreased Increased Normal
Relapse	Uncommon	Common
Treatment	Mainly supportive	Specific by Prednisolone

*Short and Long Cases in Clinical Medicine, HN Sarker; **Step on to Paediatrics, Md Abid Hossain Mollah

1. General measures
   1. Bed rest—Increases GFR, so helps in reducing hypertension
   2. Diet
      • Salt restricted diet. No added salt in the diet.
      • Protein restricted diet (0.5 gm/kg/day**)
      • Fluid (previous day urine output + 300 mL) / (400 mL/m² + previous day’s output **)
      • K⁺ containing food and fruits restriction.
2. Supportive measures
   1. Edema—Diuretic, e.g. frusemide (1-2 mg/kg/day **) (If renal function impairment, dose of diuretics is single and high. but if renal function is normal, then divided and low dose. ***)
   2. Antihypertensive drug—Calcium channel blocker, ACE inhibitor
      • For rapid reduction of BP: Nifedipine (0.3–0.5 mg/kg) sublingual **
      • For maintenance:
        • Captopril (0.25–6 mg/kg/day) in 2–4 doses **
        • Nifedipine (0.25–0.5 mg/kg/day) in 2–4 doses **
   3. Antibiotic—Phenoxymethylpenicillin/erythromycin for 10 days.
      • Oral Phenoxymethylpenicillin (50 mg/kg/day) in 4 divided doses for 10 days. Penicillin does not alter the course of the disease but prevents spreading of remaining nephritogenic strain of streptococcus to the contacts.**
3. Treatment of complications if any.
4. Follow up: Daily to assess the clinical response and to search for any complications.
   1. Pulse
   2. BP
   3. Edema
   4. Weight
   5. Maintain fluid intake output chart
   6. Albumin chart.

* Short and Long Cases in Clinical Medicine, HN Sarker; ** Step on to Paediatrics, Md Abid Hossain Mollah; ***Long Cases in Clinical Medicine, ABM Abdullah.

Preferred antihypertensives are:
– Calcium channel blocker, e.g. amlodipine
– ACE inhibitor if S.creatinine is less than 5 mg.

*Short and Long Cases in Clinical Medicine, HN Sarker

Follow up: Daily to assess the clinical response and to search for any complications.

1. Pulse
2. BP
3. Edema
4. Weight
5. Maintain fluid intake output chart
6. Albumin chart.

*Short and Long Cases in Clinical Medicine, HN Sarker

1. Complete recovery – 80% of childern and 50% of adults (usually within 2 weeks)
2. Apparent recovery – 10-15% cases live with persistent proteinuria and hematuria for long periods.
3. Complications – 5% cases develop complications e.g. Rapidly Progressive Glomerulonephritis (RPGN)

Recurrence are extremely rare.

*Short and Long Cases in Clinical Medicine, HN Sarker.

As follows:

• Acute renal failure
• Hypertension and its complications, such as
  • acute left ventricular failure,
  • hypertensive encephalopathy
• Fluid and electrolyte imbalance (↑K⁺, ↓Na)
• Nephrotic syndrome**
• May lead to chronic glomerulonephritis.**

*Short and Long Cases in Clinical Medicine, HN Sarker; Step on to Paediatrics, Md Abid Hossain Mollah; **Long Cases in Clinical Medicine, ABM Abdullah

Acute pulmonary edema due to hypertensive LVF.

Hypertensive encephalopathy.

Mechanism of nephrotic syndrome are:
– Injury to podocytes
– Changed architecture—Scarring
– Deposition of matrix or other elements.

Causes are:

1. Primary renal disease—all types of glomerulonephritis (80%):
   1. Minimal change glomerular disease (the most common in children)
   2. Membranous GN (the most common in adult)
   3. Mesangiocapillary and proliferative gomerulonephritis
   4. Focal and segmental glomerulosclerosis
   5. IgA nephropathy.
2. Secondary to other disease:
   1. Diabetic nephropathy
   2. Collagen disease, mainly SLE, also rheumatoid arthritis (by amyloidosis)
   3. Amyloidosis
   4. Drugs—penicillamine (common), captopril, gold, mercury, NSAIDs, stibogluconate.
   5. Neoplastic—carcinoma (bronchial carcinoma, ca. breast, ca. colon), lymphoma, leukemia.
   6. Infection—malaria (quartan malaria), bacterial endocarditis, HBV, HCV, HIV, secondary syphilis, leprosy, toxoplasma.
   7. Allergies—bee stings, snake bite, anti-snake venom, pollens.

*Long Cases in Clinical Medicine, ABM Abdullah;  Short and Long Cases in Clinical Medicine, HN Sarker; Step on to Paediatrics, Md Abid Hossain Mollah

– Minimal change glomerular disease
– Membranous GN
– Mesangiocapillary and proliferative gomerulonephritis

Causes are:

1. Minimal change glomerular disease (70%)
2. Mesangiocapillary and proliferative gomerulonephritis (15%)
3. Focal and segmental glomerulosclerosis (10%)

Minimal change glomerular disease is the most common in children (70%)

• Common in children, particularly male, but may occur in all ages, associated with atopy
• On light microscopy, there is no abnormality but on electron microscopy, there is fusion of podocyte foot process (flattening of the foot process)
• Selective proteinuria
• No immune deposit
• Good response to steroid and cytotoxic drugs.
• Progress is excellent, progression to renal failure is rare

*Long Cases in Clinical Medicine, ABM Abdullah; Short and Long Cases in Clinical Medicine, HN Sarker

Membranous nephropathy is the most common in adult.

• It is a common cause of NS in adult (35%), predominantly in males
• It is mostly idiopathic
• May be secondary to—SLE, bronchial carcinoma, drugs (penicillamine), heavy metals like mercury, HBV, HCV
• There is granular subepithelial IgG deposit
• Non-selective proteinuria
• Renal biopsy shows thickening of glomerular basement membrane, increased matrix deposition and glomerulosclerosis
• Response to steroid and other cytotoxic drugs is less.
• Prognosis is bad
• Renal vein thrombosis is a common complication
• May progress to CKD (10-15%)

*Long Cases in Clinical Medicine, ABM Abdullah; Short and Long Cases in Clinical Medicine, HN Sarker

Lipid abnormalities are:

• Hypercholesterolemia and hypertriglyceridemia
• High LDL, VLDL and IDL
• There is no change or low HDL.

The mechanisms are:

1. Increased synthesis of lipoproteins by the liver, secondary to hypoalbuminemia
2. Reduced clearance of triglyceride bearing lipoprotein (chylomicron and VLDL) in direct response to albuminuria.
   As a result, there is high rate of atherosclerosis.

*Long Cases in Clinical Medicine, ABM Abdullah

There is increased permeability of the glomerular capillary wall due to –

1. Reduction of fixed negatively charged protein molecules in glomerular capillary wall which repel negatively charged protein molecules, allows proteins to pass through the pores
2. Damage to the glomerular basement membrane that leads to increase in the size and number of pores, allowing passage of larger molecules.

*Long Cases in Clinical Medicine, ABM Abdullah

Previously it was thought that reduction of albumin causes low plasma oncotic pressure, which causes to edema. But recent view is oncotic pressure is not changed in NS, edema is due to sodium retention in the extracellular compartment. Also, there is change in molecular barrier, which causes edema.

*Long Cases in Clinical Medicine, ABM Abdullah

Usually blood pressure is normal, even low. If there is hypertension, usually it is secondary to underlying disease like SLE with renal involvement, polyarteritis nodosa, diabetic nephropathy or terminal stage of nephrotic syndrome.

*Long Cases in Clinical Medicine, ABM Abdullah

Usually hypertension is not a feature of NS. If present, one should consider:

• Onset of CRF
• NS in SLE
• NS in polyarteritis nodosa,
• Kimmelstiel-Wilson (K-W) syndrome (NS in DM)

*Short and Long Cases in Clinical Medicine, HN Sarker

Focal segmental glomerulosclerosis (FSGS).

Mechanisms are as follows:

1. In nephrotic syndrome, there is hypercoagulable state due to:
   • Loss of inhibitors of coagulation in urine, such as antithrombin III, protein C and S, and also loss of fibrinolytic factor (plasminogen).
   • Increase synthesis of clotting factors—factor V, VIII and fibrinogen.
   • Other factors—thrombocytosis and over diuresis resulting in dehydration, reduced renal blood flow and increased viscosity, prolonged bed ridden.
2. Also, there is hyperlipidemia, commonly high LDL, VLDL, cholesterol and triglyceride. So, there is more atherosclerosis.
   These predispose to increased venous thrombosis that occurs specially in renal vein.

*Long Cases in Clinical Medicine, ABM Abdullah.

Ans. When urinary output is less than 300 mL in a day on a normal diet.

Ans. It is the complete absence of urine production for the last 24 hours or less than 30 mL/day.

Ans. Polyuria means excessive urinary output, i.e. urine volume >3 L/day.

Ans. Causes are:

• Excess fluid intake
• Osmotic, e.g. hyperglycemia (DM) and hypercalcemia
• Cranial diabetes insipidus—Idiopathic (50%), mass lesion, trauma, and infection.
• Nephrogenic diabetes insipidus
  • Drugs/toxins, e.g. lithium and diuretics
  • Interstitial renal disease
  • Hypokalemia, hypercalcemia.

Haematuria is the presence of blood in the urine and can vary from frank bleeding (macroscopic) to the microscopic detection of red cells.

* John Murtagh’s General Practice, 6th Edition Page: 865

Haematuria is red blood cells in the urine arising from the kidneys or urinary tract.

* Macleod’s Clinical Examination, 13th Edition Page: 200

The causes of hematuria are:
– Glomerulonephritis
– Tumor
– Infection
– Infarction
– Cysts in kidney
– Stones.

* Pre-exam preparation for medicine, HN Sarker

Figure: Structure is adapted from Davidson’s Principles and Practice of Medicine, 22nd edition Page 475

Causes of hematuria are:
– Glomerulonephritis
– Urinary tract infection
– Infective endocarditis
– Infarction
– Benign familial hematuria
– Blood dyscrasia.

* Pre-exam preparation for medicine, HN Sarker

Causes of painless hematuria are:
– Glomerulonephritis
– Renal tuberculosis
– Infective endocarditis
– Benign familial hematuria
– Blood dyscrasia.

* Pre-exam preparation for medicine, HN Sarker

Causes of red urine are:

• Hematuria
• Hemoglobinuria
• Myoglobinuria
• Food dyes – For example, anthocyanins (beetroot)
• Drugs – For example,
  • Phenolphthalein—Pink when alkaline
  • Senna/other anthraquinones—Orange
  • Rifampicin—Orange
  • Levodopa—Darkens on standing
• Porphyria—Darkens on standing
• Alkaptonuria
• Bilirubinuria – For example, obstructive jaundice—Dark.

* Pre-exam preparation for medicine, HN Sarker 

Points to consider during history taking –

• Have you had an injury such as a blow to the loin, pelvis or genital area?
• Have you noticed whether the redness is at the start or end of your stream or throughout the stream?¹
• Have you noticed any bleeding elsewhere, such as bruising of the skin or nose bleed?
• Have you experienced any pain in the loin or abdomen?²
• Have you noticed any burning or frequency of your urine?
• Have you had any problems with the flow of your urine?
• Have you been having large amounts of beetroot, red lollies or berries in your diet?
• Could your problem have been sexually acquired?
• Have you been overseas recently?
• What is your general health like?
• Have you been aware of any other symptoms?
• Do you engage in strenuous sports such as jogging?
• Have you had any kidney problems in the past?
• Relevant drug history, especially with anticoagulants and cyclophosphamide.
• History of skin infection and scabies (AGN)
• History of oral ulcer, skin rash and joint pain (SLE)

¹Haematuria occurring in the first part of the stream suggests a urethral or prostatic lesion, while terminal haematuria suggests bleeding from the bladder. Uniform haematuria has no localising features.

Painful haematuria is suggestive of infection, urethral caruncle, calculi or kidney infarction, while painless haematuria is commonly associated with infection, trauma, tumours or polycystic kidneys.

²Loin pain can occur as a manifestation of nephritis and may be a feature of bleeding in cancer of the kidney or polycystic kidney.

* John Murtagh’s General Practice, 6th Edition Page: 866

As follows:

1. Urinalysis by dipstick testing (e.g. Hemastixaffected derivatives—affected by vitamin C intake). 
2. Urine microscopy:
   • formed RBCs in true haematuria
   • red cell casts indicate glomerular bleeding
   • deformed (dysmorphic) red cells indicate glomerular bleeding
3. Urinary culture:
   • early culture is important because of the common association with infection and consideration of early treatment with antibiotics.
   • If tuberculosis is suspected, three early morning urines should be cultured for tubercle bacilli.
4. Urinary cytology:
   • this test, performed on a urine sample, may be useful to detect malignancies of the bladder and lower tract but is usually negative with kidney cancer.
5. Blood tests:
   • appropriate screening tests include a full blood count, ESR and basic kidney function tests (urea and creatinine).
   • If glomerulonephritis is suspected, antistreptolysin O titres and serum complement levels should be measured.
6. Radiological and other imaging techniques—available tests include:
   • intravenous urography (IVU); intravenous pyelogram (IVP)—the key investigation
   • ultrasound (less sensitive at detecting LUT abnormalities)
   • CT scanning
   • kidney angiography
   • retrograde pyelography
7. Direct imaging techniques:
   • these include urethroscopy, cystoscopy and ureteroscopy.
   • In all patients, regardless of the IVU findings, cystoscopy is advisable.
8. Kidney biopsy:
   • indicated if glomerular disease is suspected, especially in the presence of dysmorphic red cells on microscopic examination.

* John Murtagh’s General Practice, 6th Edition Page: 867-868

Proteinuria is excess protein in urine and indicates kidney disease.

* Macleod’s Clinical Examination, 13th Edition Page: 201

Proteinuria is the presence of abnormal quantities of protein in the urine, which may indicate damage to the kidneys.*

Note:

Whilst moderate amounts of low-molecular-weight protein pass through the healthy glomerular basement membrane (GBM), these proteins are normally reabsorbed by receptors on tubular cells. In healthy individuals, less than 150 mg of protein is excreted in the urine each day. The presence of larger amounts of protein is usually indicative of significant renal disease.**

* Google dictionary; ** Davidson’s Principles and Practice of Medicine, 22nd edition Page: 476

Proteinuria occurring after long-standing is called orthostatic proteinuria.

* * Pre-exam preparation for medicine, HN Sarker

Procedure:

1. Two-thirds of a test tube is filled with urine.
2. A blue litmus paper is emmersed to test the reaction of urine.
   • If alkaline, a few drops of 5% acetic acid is added to make urine acidic.
3. Then upper portion of urine is heated to boiling and checked.

* * Pre-exam preparation for medicine, HN Sarker

Normal reaction of urine is acidic.

* * Pre-exam preparation for medicine, HN Sarker

Interpritation:

• After heating if there is cloudiness, it indicates presence of protein or phosphate.
• A few drops of acetic acid is added and heated again, phosphate will dissolve but protein intensifies.

* * Pre-exam preparation for medicine, HN Sarker

ACR1	PCR2	Typical dipstick results3	Significance
< 3.5 (female) < 2.5 (male)		–	Normal
~3.5–15		–	Microalbuminuria
~15–50	~15–50	+ to ++	Dipsticks positive; equivalent to 24-hr protein excretion < 0.5 g
50–200	> 250	++ to +++	Glomerular disease more likely
> 200	> 300	+++ to ++++	Nephrotic range: always glomerular disease, equivalent to 24-hr protein excretion > 3 g
1Urinary albumin (mg/L)/urine creatinine (mmol/L). 2Urine protein (mg/L)/ urine creatinine (mmol/L). (If urine creatinine is measured in mg/dL, reference values for PCR and ACR can be derived by dividing by 11.31.) 3Dipstick results are affected by urine concentration

* Davidson’s Principles and Practice of Medicine, 22nd edition Page: 476

As follows:

• Renal cell carcinoma
• Hydronephrosis or pyonephrosis
• Renal abscess
• Solitary kidney (due to hypertrophy) in lean and thin person.

*Long Cases in Clinical Medicine, ABM Abdullah

As follows:

• Polycystic kidney disease
• Bilateral hydronephrosis
• Amyloidosis
• Diabetic nephropathy in early stage
• Bilateral renal cell carcinoma (rare)
• Lymphoma (rare).

*Long Cases in Clinical Medicine, ABM Abdullah

The common renal diseases causing hypertension are:
– Glomerulonephritis
– Renovascular disease
– Interstitial diseases
– Renal artery stenosis
– Polycystic kidney disease.

*Pre-exam preparation for medicine, HN Sarker