Renal Failure
Renal functions include excretory, metabolic, and endocrinal functions. Renal failure is a clinical condition when kidneys fail to perform the function adequately as a result of which there is a breakdown of the homeostatic balance of fluid, electrolytes, and acid-base with an accumulation of nitrogenous waste products like BUN; creatinine, and acid metabolites in the blood resulting in uremia. In Chronic renal failure, deficiency of Vit. D, hyperparathyroidism, and erythropoietin deficiency cause renal bone disease and renal anemia.
Types Of Renal Failure
Renal failure is of 3 types viz. acute renal failure, chronic renal failure, and acute on chronic renal failure. Acute renal failure is characterized by sudden deterioration of renal function commonly associated with oligo-anuria which is a hallmark of ARF; whilst CRF presents insidiously with failure to thrive, short stature, anemia resistant to hematinics, resistant rickets- a clinical picture which can be confused with chronic malnutrition. Acute on chronic renal failure present like ARF and on investigations a preexisting renal disease is found viz. membranoproliferative glomerulonephritis, lupus nephritis, etc.
Causes Of Renal Failure
Causes of ARF- At any age, the basic mechanisms leading to ARF are:
Prerenal ARF -Due to reduced blood volume as a result of dehydration, shock, hemorrhage, cardiac failure, hypoxia, nephrotic syndrome, etc.
Intrinsic renal failure due to acute tubular necrosis which follows prolonged prerenal failure resulting in renal ischemia following acute gastroenteritis commonly. Other causes in bigger children can be acute post-streptococcal glomerulonephritis or pyelonephritis, hemolytic uremic syndrome, drugs and toxins causing tubulointerstitial injury, G-6-PD deficiency, malaria, vasculitis, bilateral renal vein thrombosis, uric acid nephropathy, sepsis or hypoxic-ischemic injury (as in asphyxia or renal artery obstruction), acute renal failure on a preexisting renal disease like lupus nephritis, IgA nephropathy or membranoproliferative G.N.
Post renal ARF whenever there is obstruction at the level of the bladder neck or urethra due to posterior urethral valves, calculi, or obstruction in the ureter of a single kidney or pelvic ureteric junction obstruction in a single kidney.
Chronic renal failure is caused broadly by chronic glomerulonephritis, chronic pyelonephritis with reflux nephropathy, obstructive uropathy, congenital anomalies of kidney like hypoplastic kidney, bilateral cystic dysplasia, infantile polycystic kidney disease, inherited diseases like Alport's disease, juvenile nephronophthisis, oxalosis, cystinosis and systemic diseases like lupus nephritis, polyarteritis nodosa, etc. The common pathology in all these diseases is relentlessly progressive destruction of nephrons as a result of a variety of diseases of the kidney and urinary tract which may culminate in end-stage renal disease over a period of months or years.
Presentation
A renal failure patient can present with salt and water retention, high BP, reduced urine output, and in severe cases breathlessness(due to acidosis/pulmonary edema/CCF), convulsions and unconsciousness due to hypertensive encephalopathy or uremic toxins.
Early Detection
Early detection helps in better management. A high index of suspicion in the clinical setting of ARF/CRF, estimation of BUN, S. creatinine whenever suspected, monitoring of urine output to detect oliguria are simple methods of early diagnosis of renal failure.
Investigations
Investigations in a case of ARF are done on an emergency basis to detect life-threatening situations like hyperkalemia, pulmonary edema, acidosis. BUN, serum creatinine, serum sodium, potassium, blood pH, bicarbonate, serum calcium, phosphorus, alkaline phosphatase, urine examination, ECG to detect cardiac arrhythmia due to hyperkalemia, x-ray chest for diagnosis of pulmonary edema and cardiomegaly are needed. Although oliguria i.e. urine output less than 1 ml/kg/day with the increase in the level of BUN >20 mg/dl and serum creatinine >1.5 mg/dl are hallmarks of diagnosis of ARF, before starting the treatment the above-mentioned investigations are necessary for the diagnosis of complications and to decide the indications of dialysis if conservative treatment fails. For the diagnosis of the cause of ARF, clinical manifestations combined with special tests like ASO titer and serum C3 levels(for diagnosis of acute post-streptococcal glomerulonephritis); ANA, anti-dss DNA(for lupus); peripheral smear for burr cells &platelet count, and coagulation studies (for diagnosis of HUS/TTP) and G-6-PD level are required. Rarely kidney biopsy may be indicated for the final diagnosis of ARF to diagnose crescentic glomerulonephritis, MPGN, IgA nephropathy, or lupus nephritis. A kidney biopsy is only indicated if the cause of ARF is not evident by clinical, biochemical, or radiological investigations.
As regards chronic renal failure, the same tests are recommended. Ultrasonography is used to assess the size of the kidney (small kidney- poor outcome). In addition, an x-ray of hands for diagnosis of renal bone disease and hematological investigations including serum ferritin levels for diagnosis of anemia due to erythropoietin deficiency is required. GFR estimation using standard endogenous creatinine clearance test or Schwartz's formula
GFR= (k x Height in cm)/Plasma creatinine
'k' is a constant which differs with age. The above formula gives an accurate measurement of renal function.
Management Of ARF
It consists of maintenance of fluid and electrolyte balance (strictly according to urine output, weight, presence of sodium and water retention), control of hypertension, treatment of hyperkalemia (with I. V. calcium gluconate + I.V. sodium bicarbonate + glucose-insulin drip, and use of ion exchange resin like kayexalate which exchanges potassium for sodium in G.I. tract and reduces blood levels of potassium. Albuterol inhalation is used for hyperkalemia recently.)
Dietetic restriction of protein, potassium, sodium, and water is the backbone of conservative management of ARF. If these measures fail, peritoneal dialysis is the treatment of choice as renal replacement therapy (RRT). The main indications of peritoneal dialysis are emergency situations like:
Treatment Of CRF
- Diet
- Conservative therapy to reduce phosphorus, use of calcitriol, erythropoietin in appropriate cases.
Conservative management can maintain good health for a few months to years. If GFR falls below 10 ml/min/ 1.73 sq.metre, renal replacement therapy (RRT) needs to be initiated. RRT consists of1 chronic maintenance hemodialysis2 chronic ambulatory peritoneal dialysis (CAPD)3 Renal transplantation which is a preferred mode of therapy.
Precautions to Both Prevent and Retard the Progression of the Disease
Prevention of ARF can be done by rapid correction of shock, dehydration, hypoxic-ischemic injury in a neonate and infants, by avoidance of drugs that are known to cause ARF, prevention of E. Coli gastroenteritis by avoiding uncooked food and contaminated milk and water because verotoxin producing E. Coli cause HUS. Prevention of CRF can be achieved by prevention and adequate treatment of recurrent urinary tract infection, by early detection of vesicoureteral reflux (VUR), correction of congenital anomalies like posterior urethral valves/pelviureteral obstruction/severe grades of VUR. Control of high BP, protein restriction in diet, use of ACE inhibitor to control proteinuria in diabetic or reflux nephropathy, use of drugs in a dosage appropriate for the renal function are some of the measures known to prevent the rapid progression of the disease.
Renal Transplant
Renal transplant is the preferred treatment for a patient with end-stage renal failure when GFR falls below 5-10 ml/min/1.73sq meter. A transplanted kidney from a healthy living donor or cadaver can fulfill all the functions of the kidney required for the normal growth and survival of a patient with ESRD.
Dialysis
Peritoneal dialysis is a procedure in which the transfer of solutes like urea, sodium, potassium, creatinine and other metabolites and water from the blood to dialysate fluid occurs across the peritoneum which serves as a semipermeable membrane. The dialysate fluid is instilled in the peritoneal cavity via a catheter which is specially designed for P.D. for infants and bigger children of various sizes. For patients with ARF, PD is required for 24-96 hours, whilst for CRF patients, chronic PD is required for which a special Tenckhoff catheter is surgically inserted in the peritoneal cavity to create permanent access. PD can be done 4-5 times/day via Tenckhoff's catheter for many years using special bags containing PD fluid.
Hemodialysis is done by creating arteriovenous connections by means of an AV shunt or fistula so that blood from the arterial side can flow alongside the dialysate fluid in a dialyzer containing bundles of a semipermeable membrane (coprophage cellulose acetate etc). Mass transfer of solute and water occurs from the blood of the patient into the dialysate fluid extracorporeally by diffusion and convection by means of a dialysis machine. Special sets of needles, tubings, dialyzers are required for pediatric patients. Hemodialysis is technically difficult in young infants due to small sizes of vessels on a long term basis. Hence peritoneal dialysis using a Tenkchoff catheter is preferable for children with chronic renal failure. Advantages of CAPD are many viz. can be done at home after a short training by the parents, fewer chances of hemodynamic instability, no disruption of school/activity, fewer visits to the hospital, no needle punctures, and less disturbance to the family. Currently high cost of dialysate fluid, tubings, etc. are responsible for less use of CAPD in Indian children with ESRD.
Erythropoietin and Other Vitamin Supplements
The role of erythropoietin is to correct erythropoietin deficiency which occurs in CRF. Erythropoietin is synthesized by the kidney and by its action on bone marrow is responsible for erythropoiesis. In CRF because of nephron loss, EPO deficiency occurs and results in normocytic normochromic anemia requiring EPO administration for its correction.
Vit D in its active form (calcitriol) is required for the treatment of renal bone disease. 25 OH Vit D is hydroxylated to 1,25(OH)2 Vit D. in the Kidney. This conversion is not possible in CRF resulting in the demineralization of bones, rickets, and renal osteodystrophy. Oral or IV calcitriol can heal the bones and prevent secondary hyperparathyroidism which is the other cause of renal bone disease.
Dietary Advise
Dietetic management is important in controlling the accumulation of nitrogenous metabolites like urea, phosphorus, potassium, sodium, and excess fluid in acute and chronic renal failure. Excess protein is harmful in chronic renal disease, as it can cause hyperfiltration and glomerulosclerosis. Protein restriction is an important measure to prevent the progression of CRF. Coconut water, Fruit juices, etc. contain potassium and hence to be avoided in ARF. Excess intake of salt and water can cause fluid and sodium retention with pulmonary edema in oliguric patients. A non-vegetarian diet is rich in proteins, phosphorus, and fat which are to be avoided in renal failure.
Drugs to Avoid In Renal Failure
Drugs that are nephrotoxic and can induce renal failure are NSAIDS, cyclosporin A, aminoglycosides, cephalosporins, indomethacin, sulpha, anticancer drugs (like cisplatinum, ifosfamide), anti-fungal agents (like amphotericin B), antiviral (like acyclovir), and radiocontrast medium. Minimum use of drugs in renal failure and modifying the dosage of drugs according to the GFR/S. creatinine levels are very essential to prevent further damage to the kidney.
Follow Up
A patient with acute renal failure needs frequent follow up with renal biochemistry, urine examination, BP monitoring at least once a week until all parameters normalize. Complete recovery may take a few months to 1 year.
Chronic renal failure should be followed with growth monitoring, BP recording, and renal function tests every 1-3 months to evaluate the efficacy of conservative therapy, till the renal function stabilizes or GFR falls to a level when renal replacement therapy needs to be initiated.
Prognosis
Prognosis of ARF depends on (a) underlying cause e.g. Acute post-streptococcal glomerulonephritis and ATN (Acute tubular necrosis)can recover fully if early diagnosis and treatment are offered. (b) Severe crescentic glomerulonephritis and HUS are associated with mortality (c) Anuria lasting for more than 3 weeks, young age, multiorgan failure, cortical necrosis, late referral are associated with high mortality (d) pre-existing renal disease like lupus, MPGN, etc. are likely to progress to end-stage renal disease years after the initial presentation as ARF.
Prognosis in a case with CRF depends on the cause e.g.congenital obstructive anomalies, congenital nephrotic syndrome, polycystic kidney disease, oxalosis, cystinosis progress to ESRD requiring RRT by 5-6 years of age, whilst chronic glomerulonephritis, chronic pyelonephritis, Alport's disease go into ESRD during adolescence and young adulthood.
There are some cases of CRF that remain with stable renal function with proteinuria and hypertension for years. They usually suffer from short stature. Growth hormone therapy is an additional treatment for short stature due to CRF. It is very expensive.
The prognosis of a patient with ESRD is poor unless there is a possibility of getting a renal transplant.
Complications
Complications of ARF: hypertension, pulmonary edema or CCF, hyperkalemia, uremic or hypertensive encephalopathy gastrointestinal bleeding, nutritional deficiency.
Complications of CRF: growth failure, renal osteodystrophy anemia, cardiac dysfunction, hypertension, neurological and developmental defects in young children.