Chronic Kidney Disease and Renal Failure

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Introduction

Chronic kidney disease is the progressive and irreversible loss of kidney function, most often leading to end stage renal disease (ESRD). The public health impact of CKD is enormous due to attending cardiovascular disease and the need for dialysis or transplant.

 

The Case of...

a simple case introducing clincial presentation and calling for a differential diagnosis to get students thinking.

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Causes and Risk Factors

Causes of end stage renal disease, with percentage distribution, are as follows:

• diabetes mellitus ~ 40%
• hypertension ~ 30%
• glomerulonephritis (rapidly progressive GN, FSGS, membranoproliferative GN, IgA nephropathy) - 10%
• interstitial nephritis or pyelonephritis - 4%
• polycystic kidney disease - 3%
• secondary glomerulonephritis or vasculitis - 2%
• miscellanous or unknown cause - 11%

Reversible causes of further renal decline should be queried and treated:

• volume depletion
• illnesses such as congestive heart failure, UTI, flu
• medications
  • NSAIDs
  • diuretics
  • ACE inhibitors and ARBs (ensure patients stop these if they are dehydrated)
  • antibiotics, especially TMP-SMX
• contrast nephrotoxicity
• obstruction due to BPH, malignancy (bladder, cervical, prostate, etc)

40% of people with a CrCl of less than 40 ml/min have received excess does of drugs.

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Pathophysiology

Chronic renal disease is initially a combination of glomerular damage, mesangial sclerosis, and tubular hypertrophy. Progressive nephron loss eventually leads to kidney shrinkage and cortical thinning.

 

Once present, renal insufficiency tends to progress, regardless of cause. Glomerular sclerosis results from hyperfiltration and/or hypertension. To ensure homeostasis, surviving nephrons increase filtration and excretion rates, leading to glomerular and tubular hypertrophy. Sodium balance is maintained by increasing fractional excretion.

 

Hyperlipidemia may play a role through mesangial proliferation and sclerosis.

Short-term adaptive mechanisms lead to long term fibrosis due to activation of the RAAS pathway and increased expression of TGFβ.

Once renal failure has set in, most glomeruli are replaced by hyaline balls and there is almost complete tubular atrophy.

Stage	Description of GFR	GFR (ml/min/1.73m2)
1	normal/increased	>90
2	mildly decreased	60-89
3	moderately decreased	30-59
4	severely decreased	15-29
5	kidney failure	<15

 

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Signs and Symptoms

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Investigations

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Differential Diagnosis

 

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Treatments

Nephrology should become involved when creatinine levels reach 120-150 umol/L. Early consultation is very important to identify and treat underlying disease and to prepare patients for dialysis or transplantation.

Early referral is associated with lower mortality, better pre-dialysis care, and is cost-effective (Yu, 2003).

 

Slowing Disease Progression

It is vitally important to slow disease progression, preserving as much urine output as is possible. Key objectives include:

• identifying and treating potentially reversible factors
• glycemic control in diabetes
• aggressive treatment of hypertension (< 130/80 mmHg) and proteinuria with ACE inhibitors and other antihypertensives (ie calcium channel blockers verapimil, diltiazem)
• avoiding nephrotoxic drugs (NSAIDs, aminoglycosides)
• pre-treat with fluids and N-acetylcysteine before contrast given for CT scans
• early referral to a nephrologist

 

Decreasing morbidity and mortality

• preventing CV disease
• managing anemia
• managing osteoporosis

 

Diet

Currently, aggressive dietary management, limiting sodium, potassium, phosphorus, and protein - appears to be useful. Dietary protein restriction - 0.60g/kg/day if possible, or 0.75g/kg/day if not - has a small impact. However, malnutrition is a strong predictor of increased mortality, and so dietary modificiations must be made with great care and followup.

 

 

Renal replacement therapy

Renal replacement therapy should be begun when GFR falls below 15 ml/min, though discussions and preprations should be made far in advance. Kidney transplantation is preferred where possible. Dialysis can be hemodialysis or peritoneal dialysis. The latter is preferable, but peritonitis and increased body mass make it less common.

 

 

Other Treatment Considerations

Drug dosing needs to be adjusted according to GFR, especially for those that are renally excreted. These include:

• digoxin
• allopurinol
• newer anticoagulants

 

 

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Consequences and Course

People with chronic renal failure are susceptible to edema and severe volume overload, hyperkalemia, hyponatremia, and azotemia. Loss of dialysis access can occur and lead to no treatment options.

 

Cardiovascular effects

Cardiovascular disease mortality is increased 3.5x in patients with renal failure. More than 60% of people beginning dialysis have left ventricular dystrophy, dilation, and systolic/diastolic dysfunction. Anemia and hypertension can also be caused by renal disease and further contribute to CVD. Secondary hyperparathyroidism can lead to hypercalcemia and calcification. Accelerated atherogenesis can lead to high rates of coronary artery disease.

Have a high index of suspicion for ACS. However, it is important to understand troponin can be increased in 20% of patients with dialysis, without ACS.

 

Gastrointestinal effects

Gastrointestinal problems are common and appear early. People with kidney failure usually describe a metallic taste and loss of appetite. Nausea, vomiting, and weight loss can all occur but are reversible with dialysis. GI bleeding can also occur via gastritis, peptic ulcers, AV malformation, and platelet dysfunction.

 

Neurologic effects

CNS manifestations are frequent. Subtle changes in cognitive function and disturbances of memory or sleep can occur. Lethargy, irritability, encephalopathy, asterixis, and seizures are late manifestations.

Peripheral neuropathy can appear with symmetrical glove-and-stocking patterns. Motor impairment can lead to restless legs or wrist drop. Decreased distal tendon reflexes and loss of vibratory perception can occur.

 

Musculoskeletal effects

Renal osteodystrophy can result from loss of vitamin D hydroxylation and altered calcium and phosphate homeostasis. Phosphate retention leads to secondary hyperparathyroidism and increased bone resorption.

 

Hematologic effects

Anemia can result from loss of erythropoietin production and iron deficiency.

 

Endocrine and metabolic effects

Altered thyroid functions can occur with uremia, and goiter is present in up to 1/3 of cases. Disruption of the pituitary-gonadal axis can lead to sexual dysfunction, amennorhea, sterility, and uterine bleeding.

 

Loss of nephrons can lead to retention of ions such as sulfates, leading to anion gap metabolic acidosis.

 

Decreased insulin clearance can lead to frequent hypoglycemia in people with diabetes, although insulin resistance also does occur.

Type IV hyperlipoproteinemia is common, contributing to increased atherosclerosis.

 

Immunologic effects

Problems with both humoral and cellular immunity occur, leading to immunosuppression and increased risk of infections.

 

Dermatologic effects

Uremia can give the skin a yellowish colour, likely due to lipochromes and carotenoids. Pruritus is common, Half-and-half nails and splinter hemorrhages can occur, and the skin may become thickened and fibrosed.

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Resources and References

Yu HT. 2003. Progression of renal failure. Archives Internal Medicine. 163:1417-1429.

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Topic Development

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