Dialysis Technology: Application of dialysis in acute renal failure !

Our kidneys are destined to perform excretory as well as regulatory function to maintain a state of homoeostasis in our body. Acute renal failure (ARF) is a syndrome defined as sudden or rapid loss of renal function (kidney function) leading to accumulation of urea and creatinine (nitrogenous waste compounds). If hyperbolic relationship between plasma creatinine or urea and glomerular filtration rate (GFR) is observed after investigations, the diagnosis is established as ARF. The early clinical signs of ARF/uremia are anorexia, nausea, vomiting, and sometimes pericarditis also. The ARF is an implication of loss of more than 50% of renal function. Dialysis should be instituted whenever early signs of uremia (elevated levels of urea in the blood) are present. Cases of metabolic acidosis as well as electrolyte and fluid imbalance also need dialysis for the reversal of hemodyanmics to normal.

Dialysis is a procedure for artificially purifying the blood of a patient through meticulous surgical intervention and electromechanical equipment. No specific elevated value of plasma creatinine or urea could be regarded as critical. The fluid intake and nutritional requirements are taken into consideration for deciding the timing and mode of dialysis. Cases of ARF should be put on dialysis without much delay for the successful recovery of their renal function. However, cases of chronic renal failure (CRF) may be kept in waiting. The dialysis procedure is of two types: i)  Hemodialysis (where patient's blood is passed through artificial kidney in conjunction with dialysis solution) and ii)  Peritoneal dialysis (where dialysis fluid is passed through the abdominal peritoneal cavity of the patient). The technique of dialysis was established long back in USA by Dr. Alan P Kendal, who also patented a 'suitcase kidney' in 1978.

Conventional hemodialysis remains the preferred and the best mode of dialysis. The hemodialysis is ideal for non-hypotensive and hemodynamically stable patients. Peritoneal dialysis is probably less effective in patients with hypercatabolic disorder and/or with undiagnosed abdominal disease. Peritoneal dialysis should be avoided in patients with recent abdominal surgery. The surgical intervention for hemodialysis can be in the following ways: i)  Continuous arteriovenous hemofiltration (CAVH), ii)  Continuous arteriovenous hemofiltration with/without concomitant dialysis (CAVHD), iii)  Continuous veno-venous filtration (CVVHD). These hemodialysis techniques are simpler, safe and very effective. The biochemical recovery is monitored during the dialysis for needful correction of fluid and electrolytes. After successive dialysis sessions the patient would return to normal health.

Diabetic Renal Disease

Diabetes is a multidisciplinary disease, as many systems may need medical care. Optimal control of blood glucose level is essential to prevent diabetic complications like neuropathy, diabetic renal disease (diabetic nephropathy) and diabetic disease of eyes (diabetic retinopathy). There may also vascular and cardiac complications associated with diabetes in some patients. Diabetes may be insulin dependent (type-I) or non-insulin dependent diabetes mellitus (NIDDM or type-II diabetes). Diabetic patients develop progressive thickening of glomerular basement membrane (GBM) of glomerular capillaries along with widening of mesangium in majority of glomeruli of their kidneys. The unusual thickening of GBM and widening of mesangial area of the bundles of glomerular capillaries lead to narrowing down of functional lumen of these capillaries, there by causing pathophysiological change in the glomerular function affecting the glomerular filtration rate (GFR). Ultrastructural features of glomerulus affected by diabetes have been illustrated in Figure-1b below in comparison to normal features depicted in Figure-1a at the same magnification.

Figure-1a: Electron micrograph of a portion of the tuft of a normal glomerulus depicting normal GBM: glomerular basement membrane, Mes: mesangial area, EpC: epithelial cells or podocytes, CL: capillary lumen and US: urinary space.

Figure-1b: Electron micrograph of a portion of the tuft of a glomerulus affected by diabetes, depicting thickened GBM: glomerular basement membrane, Mes: mesangial area (widened), EpC: epithelial cell or podocyte, CL: capillary lumen (narrowed down) and US: urinary space. Note: Just compare the feature with the electron micrograph shown in figure-1a.

Uncontrolled diabetes may lead to global sclerosis of glomeruli resulting in 'end stage renal disease' (ESRD) or renal failure. Retinopathy, neuropathy and vascular and/or cardiac disease accompanying ESRD may complicate the management of prospective patients. So, diabetic patients are advised to comply sincerely with the advice of general physician or diabetologist to avoid diabetes associated complications, otherwise they may require the consultation of a nephrologist, ophthalmologist and cardiologist to manage the complications. The treatment of diabetes associated renal disease should ideally be introduced when 'traces of albumin in urine' (microalbuminuria) and polyuria (increased urine output) are detected in diabetic patients. Optimal control of diabetes by insulin and/or diet and exercise is must to avoid complications. Once massive proteinuria (excretion of >3.5 g protein per 24 hours) is developed in diabetic patients, the cost of reversal of complications may be many times higher. Just be health conscious and stay healthy & live-long.

IgA Nephropathy as a cause of End Stage Renal Disease

There are a variety of causes of end stage renal disease (ESRD) in teenagers and adults. Immunoglobulin-A (IgA) nephropathy could be a cause of end stage renal disease (ESRD) in around 25% of cases. There are five types of immunoglobulins in our body for protection against microorganisms and IgA provides defence at mucous membranes. Colostrum and breast milk are rich sources of IgA and protect us during infancy through breast-feeding. However, later in life, chronic mucosal inflammation (inflammation of respiratory, oral, or gastrointestinal mucous membranes) may lead to IgA-nephropathy (IgAN). Viral (including HIV), bacterial, yeast and parasitic infections have been found to be associated with IgAN. Environmental and food antigens have also been implicated in IgAN as these may mimic molecular structure of microbial antigens and lead to excessive IgA production, aggregation and breakdown of mucosal barrier. Patients affected by IgAN may present with hematuria (blood in urine) and/or proteinuria (protein in urine) with or without rise in serum creatinine. The most common initial symptom in children is microscopic hematuria. Some adults may present with acute or chronic renal failure.

IgA nephropathy is a common nephropathy, which could be detected on renal (kidney) biopsy evaluation through light and fluorescence microscopy. However, electron microscopic study of renal biopsy acts as a diagnostic adjunct as the location of immune complexes in the renal glomerulus could be pronounced on electron micrographs. Figures 1 and 2 are the electron micrographs from a proven case of IgAN, illustrating mesangial deposits of IgA.

Figure-1: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 4600x.

Figure-2: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 6000x.

The pathology of IgAN may be variable depending on underlying cause. Mesangioproliferative glomerulonephritis is the most common pattern in many renal biopsies; however, glomeruli may appear normal on light microscopy in some of the cases. Renal biopsies in a few cases may also show crescent formation in occasional glomeruli. Diagnosis of IgA nephropathy is established by direct immunofluorescence technique on renal biopsies and the pattern may be dominant or co-dominant for IgA staining. The incidence of ESRD has been found to be high in patients presenting with >1g/day proteinuria with increased level of serum creatinine as compared to those having proteinuria <1g/day with increased level of serum creatinine. Pathogenesis of IgAN is very complex. A variety of underlying diseases including hepato-biliary disease can be associated with IgA nephropathy. Defective detection and clearance by liver of polymeric immune complexes of IgA (IgA1) due to abnormal galactosylation of O-linked glycans is probably the major cause of IgAN in addition to loss of mucosal barrier and chronic mucosal inflammation. Recurrent tonsillitis may also lead to IgA nephropathy and tonsillectomy may be helpful in these cases to remove the mucosal foci of infection. Optimal treatment of tonsillitis and other oromucosal infections with antibiotics along with conventional treatment of IgAN would be helpful to put brakes on the progression of IgA nephropathy. Patients with acute or chronic renal failure due to advanced stage of IgAN may need hemodialysis or renal transplantation. Use of anti-oxidants and fish oil as food supplements in some cases of IgA nephropathy have been found beneficial.

End Stage Renal Disease and Renal Transplantation

Chronic glomerulonephritis, diabetic nephropathy, chronic tubulointerstitial disease, benign nephrosclerosis and polycystic kidney disease are the major causes of end stage renal disease (ESRD) and renal failure. Patients with ESRD exhibit a variety of abnormalities in their autonomic functions. Precise mechanisms of evaluating autonomic functions have revealed abnormalities in efferent parasympathetic pathway and baroreceptor sensitivity in patients with end stage renal disease. An increase in expiration-inspiration, lying standing and valsalva ratios, and baroreceptor sensitivity slope have been well documented in ESRD. Uremic patients with ESRD respond poorly to antihypertensive drugs as compared to otherwise healthy controls. Renal involvement in multiple myeloma is an other cause of ESRD and renal failure. Dialysis is an adoptive procedure in patients having end stage renal disease and ultimate surgical measure is renal (kidney) transplantation. Adequate dialysis in patients with ESRD reverses the elevated levels of urea, creatinine and electrolytes in blood.

Though renal transplantation is must in patients with ESRD, but it needs a lot of medication and post transplantation care for the successful adoption and survival of renal allograft. Systemic fungal infections (cryptococcosis, mucuromycosis, candidiasis, aspergillosis and mixed infections) have been documented after renal transplantation. Though these infections are treatable but may complicate the post operative care as additional medication will be required in addition to immunosuppressive therapy. High incidence of tuberculosis has also been observed in recipients of renal transplant along with viral infections like BK virus and cytomegalovirus (CMV). Adverse impact of pre-transplant polyoma virus (BK virus) infection on the graft survival has also been documented. Molecular technology has been developed for the early detection and identification of these viruses from the time of renal transplantation onwards by using protocol biopsies from the grafted kidney.

Kidney Diseases and Elevated Levels of Blood Urea, Uric Acid and Creatinine

There could be minimal to gross impairment of renal function during the onset and progression of a kidney disease or renal disorder. This impairment of renal function may range from subclinical to complete renal failure. Urine analysis and blood biochemistry have been of great help in the assessment of renal function. Simultaneous increase in the levels of blood urea and uric acid has been observed during a variety of renal disorders. Uric acid is an end product of purine (a component of nucleic acids and nucleoproteins) metabolism. The level of uric acid in the blood depends on its endogenous production through purine metabolism as well as from the exogenously taken purines in the food items. Normal range of uric acid in blood is 2 - 6mg/dl. Elevated level of uric acid is also observed in gout. Urea is an end product of protein metabolism and its normal range in blood is 20 - 40mg/dl.

Formation of Urea: The amino acids derived by the digestion of proteins of the food we eat are absorbed by the villi of the small intestine and brought to the liver through the portal vein. The essential amino acids required for the growth and repair of body tissues are passed on to the blood circulation by the liver and others are used to produce the blood proteins and useful proteins for the body. Useless proteins are broken down in the liver to form bioenergy composed of carbon, hydrogen and oxygen and a waste product urea. Urea is a water soluble substance and carried away buy the blood stream.

The uric acid level may increase earlier than the blood urea level during the course of renal disease. The serum uric acid could be found markedly increased from the normal level of 2 -6mg/dl to 10 - 30mg/dl with minimal impairment of renal function. The creatinine level in blood starts rising after 2 to 4 fold rise in the blood urea level. The level of urea may rise in a variety of conditions, but increased level of creatinine is considered more severe than the increased level of blood urea. The creatinine is derived from the creatine and is a waste product; on the other hand the creatine is necessary for the muscle contraction and is related to the phosphocreatine breakdown. The normal level of creatinine in the blood plasma or serum is 1 - 2mg/dl and its normal daily excretion ranges from 1 to 2 grams. The serum creatinine values of up to and even exceeding occasionally 20mg/dl have been seen in the later stages of renal failure. The major cause of increased levels of serum creatinine and blood urea is the poor clearance of these substances by the kidneys rather than excessive production. In acute glomerulonephritis values from normal to over 300mg/dl are generally observed. In conditions such as malignant hypertension, chronic pyelonephritis and heavy metal poisoning 10 to 15 fold increase in blood urea level may be detected. However, in cases of hypoadrenalism (Addison's disease) blood urea level of about 100mg/dl could be detected. Fifteen to 20 fold increase in the level of blood urea (i.e. a level of 600 - 800mg/dl) may lead to uremic coma in more than 80% cases of cases affected by severe renal disease or renal failure.