Nephrology Week 6 Summary

Question 26

List the causes of secondary hypertension. What tests could you order to assess for these diagnoses?

Secondary hypertension is elevated blood pressure that results from an underlying, identifiable, often correctable cause. Only about 5 to 10 percent of hypertension cases are thought to result from secondary causes.

The secondary causes for hypertension can be classified as follows:

  • Renal disease.
    This may be due to renovascular disease from renal artery stenosis or fibromuscular dysplasia. A clue to this may be acute elevation in serum creatinine after ACE inhibitor or angiotensin II receptor blocker. These can be assessed with renal artery doppler ultrasound, MR angiography and CT angiography. Primary renal disease can also cause hypertension.Look for elevated serum creatinine, hematuria/proteinuria on urine dipstick, and RBCs and RBC casts on urinalysis.
  • Endocrine causes.
    The endocrine disorders that may cause hypertension include:

    • Cushing’s syndrome (elevated 24 hour urine cortisol excretion, loss of normal suppressibility of cortisol secretion by the administration of low dose dexamethasone)
    • Pheochromocytoma (increased urinary catecholamine and metanephrine excretion, elevated plasma free metanephrines)
    • Primary hyperaldosteronism (elevated plasma aldosterone to plasma rennin activity ratio)
    • Primary hyperparathyroidism (elevated serum calcium and PTH)
  • Drugs.
    There are many drugs that can cause hypertension. A few examples are:

    • Oral contraceptives
    • Cocaine
    • Monoamine oxidase inhibitors
  • Coarctation of the aorta.
    May be considered in the setting of hypertension in the upper extremities but low blood pressure in the lower extremities and/or decreased femoral pulses.This diagnosis can be suggested on chest x-ray and diagnosed with echocardiography.
  • Pregnancy.
  • Sleep apnea.
    If suspect from history or physical, this can be assessed with a formal sleep study.

Question 27

What are the 3 primary glomerular diseases that cause nephrotic syndrome, and name 3 secondary causes of each?

The term nephrotic syndrome refers to a distinct constellation of clinical and laboratory features of renal disease. It is specifically defined by the presence of:

  • Heavy proteinuria (>3.5 g/24 hours)
  • Hypoalbuminemia
  • Peripheral edema
  • Hyperlipidemia

Thrombotic disease may also be observed.

The classification is based on pathological findings:

  • minimal change disease
  • focal segmental sclerosis (FSGS)
  • membranous nephropathy

Sometimes there can be associated secondary diseases that may be causative in nature.

Minimal change:

  • Drugs: NSAIDs, ampicillin, lithium
  • Cancer: Hodgkin’s lymphoma, other lymphoproliferative diseases
  • Toxins: mercury, lead, bee stings
  • Infection: mononucleosis, HIV, immunizations


  • Unilateral renal agenesis
  • Renal ablation – remnant kidney
  • Sickle cell disease
  • Morbid obesity
  • Heroin nephropathy
  • HIV nephropathy
  • Pamidronate
  • Vesicoureteral reflux


  • Immunologic disorders eg. SLE, RA, MCD
  • Neoplasms e.g. Carcinoma (lung, colon, breast etc.), melanoma, leukemia, lymphoma
  • Infections e.g. Hepatitis B, syphilis, malaria
  • Medications e.g. Penicillamine, gold, captopril

Question 28

A patient presents with hemoptysis and acute renal failure. What would be included in the differential diagnosis?

This presentation suggests the presence of a pulmonary-renal syndrome, which is a combination of acute glomerulonephritis with alveolar hemorrhage.

The pulmonary-renal syndrome can be caused by a variety of conditions, including Goodpasture’s syndrome which is associated with autoantibodies to the glomerular and alveolar basement membranes, and various forms of primary systemic vasculitis associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCA), such as microscopic polyangiitis, Wegener’s granulomatosis and, less commonly, Churg-Strauss syndrome. This syndrome can be seen less commonly in association with systemic lupus erythematosus, systemic sclerosis, antiphospholipid syndrome, drugs (including propylthiouracil and hydralazine), Behçet’s disease, Henoch–Schönlein purpura, IgA nephropathy and mixed cryoglobulinaemia.

The majority of cases of pulmonary-renal syndromes are associated with ANCAs. The antigen targets in ANCA-associated disease are proteinase-3 and myeloperoxidase. The antigen target in Goodpasture’s syndrome is the alpha-3 chain of type IV collagen.

For a more detailed, free full text review try:

Bench-to-bedside review: Pulmonary–renal syndromes – an update for the intensivist. Critical Care 2007, 11:213

Question 29

What are the stages of diabetic nephropathy? (GFR/clinical)

Name 2 trials that show the benefit of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) in delaying the progression of diabetic kidney disease.

Stage I: onset of diabetes, functional changes – increased GFR, increased kidney size, reversible albuminuria

Stage II: structural changes – increased GBM thickness, mesangial expansion

Stage III: early nephropathy – microalbuminuria, rising BP

Stage IV: onset of proteinuria, rising serum creatinine

Stage V: end stage renal disease (ESRD)

ACE inhibitor:
Examined the effect of the administration of placebo or captopril to patients with type 1 diabetes with overt proteinuria and a plasma creatinine concentration equal to or greater than 1.5 mg/dL (132 µmol/L). The likelihood of a doubling of the plasma creatinine concentration was reduced by more than 50 percent in the captopril group.


In the Irbesartan Diabetic Nephropathy Trial (IDNT), 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan (300 mg/day), amlodipine(10 mg/day), or placebo.

At 2.6 years, irbesartan was associated with a risk of the combined end point (doubling of the plasma creatinine, development of end-stage renal disease, or death from any cause) that was 23 and 20 percent lower than with amlodipine and placebo, respectively, and the values were 37 and 30 percent lower for doubling of the plasma creatinine. These benefits were independent of the differences in the magnitude of blood pressure reduction among the groups.

In the RENAAL trial, 1513 patients with type 2 diabetes and nephropathy were randomly assigned to losartan(50 titrating up to 100 mg once daily) or placebo, both in addition to conventional antihypertensive therapy (but not ACE inhibitors).

Compared to placebo, losartan reduced the incidence of a doubling of the plasma creatinine by 25 percent and end-stage renal disease by 28 percent; the mean follow-up was 3.4 years. These benefits were again not associated with differences in blood pressure levels between the groups.

Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462.

Lewis EJ et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60.

Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9.

Question 30

If a patient presents with nephrolithiasis and the following urinalysis, what type of stone would you suspect? How would you manage this patient?


Calcium oxalate dihydrate – enveloped shaped crystals

Calcium oxalate monohydrate – dumbbell, spindle shaped crystals

The mainstain of treatment of calcium oxalate stones is to increase fluid intake to reach the goal of at least 2 L of urine output per day. A reduction in calcium excretion by a low sodium diet (80-100 meg/day) may also be suggested. Low sodium excretion will enhance proximal sodium and calcium absorption, thereby decreasing urinary calcium excretion and stone formation.

Drug therapy can also be added depending on the cause. If there is hypercalciuria, thiazide diuretics may be helpful. Potassium citrate can be used in cases of hypocitraturia and type 1 renal tubular acidosis. For hyperuricosuria, treatment of choice would be allopurinol or potassium citrate.

For additional information, try this free full text reference:

Ross Morton, Eduard A. Iliescu, and James W.L. Wilson. Nephrology: 1. Investigation and treatment of recurrent kidney stones. CMAJ, Jan 2002; 166: 213 – 218

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