Chronic Kidney Disease


Chronic kidney disease (CKD) is defined as a chronic reduction in the glomerular filtration rate (GFR), resulting in a GFR <60 ml/min/1.73m2. More than 660 thousand Americans have kidney failure, with a global prevalence of 11-13%.

The progression of CKD can lead to end-stage renal disease (ESRD), which has to be managed with renal-replacement therapy or kidney transplantation. CKD is also associated with a higher risk of cardiovascular disease, cancer, and infection.

CAUSES:

Hypertension
Diabetes mellitus
Polycystic kidney disease
Atherosclerosis
Renal artery stenosis
Vesicoureteral reflux + Urinary tract obstruction
Glomerulonephritis or Interstitial nephritis
Nephrotoxins

CLASSIFICATION/STAGING:

The Kidney Disease Outcomes Quality Initiative (KDOQI) classifies CKD in different stages as follows:

Stage 1 = Normal or increased GFR but some evidence of kidney damage (e.g. microalbuminuria, proteinuria, hematuria).
Stage 2 = GFR 89 – 60ml/min/1.73m2 with some evidence of kidney damage (e.g. microalbuminuria or hematuria).
Stage 3 = GFR 59 – 30ml/min/1.73m2
Stage 3a = GFR 59 – 45 ml/min/1.73m2
Stage 3b = GFR 44 – 30 ml/min/1.73m2
Stage 4 = GFR 29 – 15 ml/min/1.73m2
Stage 5 = GFR <15ml/min/1.73m2

The degree of albuminuria can also be divided in different stages.

A1 = 300mg/day
A2 = 30 – 300mg/day
A3 = >300mg/day

DIAGNOSIS:

Careful history and physical examination should be obtained. Often CKD is completely asymptomatic at the beginning, with symptoms such as edema, hypertension and decreased urine output appearing only late in the course.

CBC, CMP and urinalysis should be obtained. Quantification of urinary albumin is also important. Ultrasound should also be obtained to rule out obstruction. Other tests may be necessary depending on the suspected cause (e.g. protein electrophoresis, ANA).

If urinalysis shows albuminuria or glomerular bleeding and the diagnosis is not obvious, a kidney biopsy may be necessary.

TREATMENT:

As soon as CKD is identified, measures to retard the progression should be adopted. GFR loss without intervention is usually 4-10ml/min/1.73m2 per year.
The progression may be retarded by controlling the BP in hypertensive patients, controlling the glycaemia in DM patients and using medications that reduce the proteinuria (ACE inhibitors or ARBs). Other treatments include sodium restriction (some suggest a protein intake of 0.7g/kg/day).

Reversible causes of CKD (hypovolemia, nephrotoxic drugs, urinary tract obstruction) should be identified and managed immediately.

Parallel to the treatment of reversible causes and measures aimed to retard progression, a vital part of the CKD management is the treatment of CKD complications.

Low potassium diet (<40-70mEq/day or 1500-2700mg/day) and the avoidance of medications that may increase the potassium (such as NSAIDs) is important to avoid hyperkalemia.

Retention of phosphate is also a common problem in CKD and it can lead to secondary hyperparathyroidism. Phosphate restriction (~900mg/day) can be tried since a lot of phosphate is found in processes foods and cola sodas. Phosphate binders may also be used. These phosphate binders can be noncalcium-containing (e.g. sevelamer – RENAGEL or RENVELA, 800-1600mg TID with meals OR lanthanum carbonate – FOSRENOL – 750-1500mg TID with meals) or calcium-containing (e.g. calcium carbonate or calcium acetate). The ones with calcium may be preferred in patients with hypocalcemia. The noncalcium-containing ones may be preferred in patients with normo or hypercalcemia.

Anemia is common among CKD patients. After excluding other causes of anemia (by ordering serum iron, TIBC, transferrin saturation, ferritin, reticulocyte count, B12 and folate concentrations), CKD anemia may be treated in patients when levels of Hb fall bellow 10g/dL (as long as transferrin saturation is >25% and ferritin >200ng/mL). Medications include erythropoiesis-stimulating agents – ESAs (e.g. epoetin alfa – EPOGEN, PROCRIT – 50 – 100U/kg subcutaneous 3x/week OR darbepoetin alfa – ARANESP – 0.45mcg/kg once a week or 0.75mcg/kg every 2 weeks). The IV route is preferred for patients on hemodialysis. The target Hb level is around 10-11.5g/dL.

Patients with CKD and metabolic acidosis may receive sodium bicarbonate 0.5/1mEq/kg/day (sodium bicarbonate oral tablet of 650mg = 7.7mEq of sodium and bicarbonate, the total daily dose can be divided in three intakes). This approach may retard disease progression. Serum bicarbonate level should be titrated to 23-20mEq/L.

Patients with late stage 4 CKD (GFR <20-25mL/min/1.73m2) should be referred to a vascular surgeon to obtain a stable vascular access for hemodialysis. The best access is an AV fistula, followed by an AV graft. Cuffed tunneled catheters may be used for intermediate duration during the maturation of a fistula or graft (which can take 4-6 weeks) or for long term in patients that are not candidates for other access.

Dialysis should be considered acutely when one or more of the following is present: fluid overload that does not respond to diuretics, uremic symptoms (pericarditis, pleuritic, nausea, vomiting, bleeding, encephalopathy), acidosis, and hyperkalemia.

Patients should be referred for a transplantation center as soon as their GFR falls below 30mL/min/1.73m2.

SOURCES & FURTHER READING:

  1. Hill NR et al. Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis. PLoS One. 2016; 11(7): e0158765.
  2. National Kidney Foundation. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification and Stratification. Am J Kidney Dis 39:S1-S266, 2002 (suppl 1).
  3. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Volume 3 | issue 1 | JANUARY 2013.