Systemic complications of chronic kidney disease

Systemic complications of chronic kidney disease

Pinpointing clinical manifestations and best managementGregorio T. Obrador, MD, MPH; Brian J. G. Pereira, MD, MBAVOL 111 / NO 2 / FEBRUARY 2002 / POSTGRADUATE MEDICINEKidneys play an essential role in the maintenance of normal homeostasis. A variety of diseases may affect the kidneys and lead to progressive nephron loss. As kidney function deteriorates, loss of excretory, regulatory, and endocrine function takes place, and complications develop in virtually every organ system. Despite the diversity of causes, the pathophysiology and clinical manifestations of progressive kidney disease are quite similar across the spectrum.

Stages of kidney disease

Glomerular filtration rate (GFR) is accepted as the best index of overall kidney function in health and disease. Several stages of CKD, defined as structural abnormalities of the kidney that can lead to decreased GFR, are recognized.

Kidney damageThis stage is defined as the presence of structural or functional abnormalities of the kidney, initially without decreased GFR, which over time can lead to decreased GFR.

Mild reduction in GFR (60 to 89 mL/min/1.73 m2)At this stage, patients usually have hypertension and may have laboratory abnormalities indicative of dysfunction in other organ systems, but most are asymptomatic. If the serum creatinine level is elevated, it may be no more than borderline and of equivocal significance.

Moderate reduction in GFR (30 to 59 mL/min/1.73 m2)This stage is characterized primarily by the presence of azotemia, defined as the accumulation of the end products of nitrogen metabolism in the blood and expressed by an elevation in serum creatinine and serum urea nitrogen (SUN) concentrations. Erythropoietin production decreases, and laboratory abnormalities reflecting dysfunction in other organ systems are usually present. Although patients may have symptoms, they often remain remarkably asymptomatic even though their kidney function may be reduced by as much as 70%.

Severe reduction in GFR (15 to 29 mL/min/1.73 m2)In this extremely tenuous stage of CKD, the worsening of azotemia, anemia, and other laboratory abnormalities reflect dysfunction in several organ systems. However, patients usually have mild symptoms.

Kidney failure (GFR, 100 ng/mL; iron saturation, >20%)

DosageDispense initial dose of 50-100 U/kg SQ once or twice per weekIncrease dose to achieve target hematocrit level between 33% and 36%Monitor hematocrit and hemoglobin levels every 1 to 2 weeks initially and after a major change in doseAs follow-up, monitor hematocrit and hemoglobin levels every 4 to 12 weeks or when indicated clinicallyMonitor iron stores and provide adequate amounts of iron

Side effects (% of patients)*Hypertension (17% to 65%)Headache (15%)Influenzalike syndrome (5%)

Causes of resistanceIron deficiency (most common)Chronic inflammationOccult malignancyAluminum toxicitySevere hyperparathyroidismMalnutrition

*Side effects of erythropoietin are unlikely to hasten progression of decline in glomerular filtration rate if blood pressure control is adequate.

Although white blood cell count is usually within normal range when CKD is present, the function of these cells may be defective, leading to an increased susceptibility to infections (20). Other common effects include an increased capillary fragility and bleeding tendency resulting from defective platelet function.

Bone diseaseMetabolism of calcium and phosphorus is abnormal in patients with CKD and is associated with the development of bone disease. Phosphate retention occurs as GFR declines. Both hyperphosphatemia and, more important, reduction in the active form of vitamin D (1,25-dihydroxycholecalciferol) lead to hypocalcemia. (The active form of vitamin D is normally produced by the kidney and increases calcium absorption in the intestine.) As attempts are made to normalize the serum calcium level, secondary hyperparathyroidism can develop, causing significant bone damage (figure 1) to occur (21,22).

The spectrum of bone disease, also known as renal osteodystrophy, includes osteitis fibrosa, osteomalacia, and adynamic bone disease. The most common form is osteitis fibrosa caused by secondary hyperparathyroidism. Although initially asymptomatic, osteitis fibrosa can produce bone pain, pathologic fractures, and metastatic calcifications in its more advanced stages. The complications associated with hyperparathyroidism can be prevented or minimized by controlling hyperphosphatemia and by lowering the parathyroid hormone level (table 3) (23).

Table 3. Treatment of abnormal calcium and phosphorus balance in chronic kidney disease

General goals

Treatment is directed first at control of hyperphosphatemia and thereafter at control of PTH secretion.

Hyperphosphatemia

The goal is to maintain serum phosphate levels in the upper range of normal (4.5-5.5 mg/dL [1.5-1.8 mmol/L]).

A low-phosphorus diet (