The lowdown on renal disease

The three main functions of the kidneys are the excretion of waste, the maintenance of extracellular fluid volume and hormone synthesis.

Acute renal failure is diagnosed when renal excretory function declines over hours or days and is potentially reversible. It is usually recognised when biochemical testing reveals that blood levels of urea and creatinine are rising, more or less rapidly. There are many causes: medical, surgical, traumatic, obstructive and obstetric. Chronic renal failure (CRF) is diagnosed when renal excretory function declines over months to years and is irreversible and the most common cause of CRF is diabetes mellitus.

The prevalence of moderate CRF (creatinine 200-500Tmol/L) is about three times greater than end-stage renal failure (ESRF). Patients with ESRF (creatinine >500umol/L) require either long-term renal replacement treatment (haemodialysis) or renal transplant in order to survive. Haemodialysis remains the default therapy for all end stage renal failure. Despite the success of transplantation and peritoneal dialysis, haemodialysis continues to have the highest rate of growth of all treatment modalities

Diagnosis of both acute and chronic renal failure depends on a plasma or serum renal profile, which commonly consists of several of the following: urea, creatinine, sodium, potassium, chloride, bicarbonate, phosphate and uric acid. Once the diagnosis of renal failure is made, such profiles are required on a regular basis. In ESRF, analysis of the dialysis fluid for analytes, for example, creatinine and urea, is often employed to ensure that the dialysis process is efficient.

The following are the Renal Association standards for ESRF:

• Pre-dialysis serum potassium should be between 3.5 and 6.5mmol/L in haemodialysis patients. Serum potassium should be between 3.5 and 5.5mmol/L in peritoneal dialysis patients.
• Pre-dialysis serum bicarbonate, measured with minimal delay after venepuncture, should be between 20 and 26mmol/L. For peritoneal dialysis patients serum bicarbonate, measured with minimal delay after venepuncture, should be between 25 and 29mmol/L.
• Serum phosphate (measured pre-dialysis in haemodialysis patients) should be below 1.8mmol/L.
• Serum calcium, adjusted for albumin concentration, should be between 2.2 and 2.6mmol/L, measured pre-dialysis in haemodialysis patients and peritoneal dialysis patients.
• Serum albumin should be measured regularly. A serum albumin concentration below 35g/L, using a Bromocresol Green assay, or below 30g/L using a Bromocresol Purple assay, should prompt clinical reassessment of the patient, looking for fluid overload, malnutrition, under dialysis, and remediable causes of an acute phase response.
• Parathyroid hormone concentrations should be less than four times the upper limit of the normal range of the assay used in patients being managed for chronic renal failure or after transplantation and in patients who have been on haemodialysis or peritoneal dialysis for longer than three months.
• Serum aluminium concentration should be measured every three months in all patients on haemodialysis and in all peritoneal dialysis patients receiving oral aluminium hydroxide. No patient whose ferritin level is >100 mg/L should have a serum aluminium concentration > 60mg/L (2.2mmol/L).
• Patients with chronic renal failure should achieve a haemoglobin concentration of ?10g/dl within six months of being seen by a nephrologist, unless there is a specific reason such as blood loss, folate or vitamin B12 deficiency. Patients must be iron replete to achieve and maintain target haemoglobin whether receiving erythropoietin or not. A definition of adequate iron status is a serum ferritin >100?g/l and <10% hypochromic red cells (transferrin saturation >20%).

Renal transplantation remains the most successful, economical and hence cost effective treatment for suitable patients with ESRF. Various immunosuppressive regimens involving mono, double or triple therapy using Prednisolone, Azathioprine, Cyclosporin microemulsion (Neoral TM), Tacrolimus, Mycophenolate mofetil or Rapamycin are employed with appropriate therapeutic drug monitoring.

Cardiovascular disease (CVD) is a prominent cause of premature death in dialysis patients. There is an increased risk in the younger patient compared to the general population, to the extent that a 35-year old haemodialysis patient has the same risk of death from CVD as an 80-year old in the general population. Hyperlipidaemia is common in dialysis patients, the pattern being an elevated triglyceride, low HDL-Cholesterol but variable changes in LDL-Cholesterol and total cholesterol that are highly dependent on nutrition, comorbidity and dialysis modality.

Other common diseases affecting the kidney include the formation of renal stones and nephropathy/proteinuria. In addition to a renal profile, serum or plasma levels of calcium uric acid and urinary levels of calcium, phosphate, sodium, potassium, bicarbonate, magnesium, creatinine, urate, oxalate, citrate, cystine, pH and creatinine clearance may be of interest in the investigation of renal stones. Should a problem be discovered, the analyte in question may be monitored to see the response to therapy. With nephropathy/proteinuria, urinary total protein and creatinine are essential for the investigation and monitoring.