Diagnosis and Type of Kidney Disease – Investigations and interpretations

Correlation of clinical and laboratory features is must for an accurate diagnosis and type of a kidney disease (renal disease) or glomerulonephritis. An experienced nephrologist can make a diagnosis of glomerulonephritis from thorough history, physical examination, urine examination and microscopy of urinary sediment. The assessment of presenting features of the patient, such as nephritic or nephrotic syndrome is important. However, the decision on the type of glomerulonephritis can not be based on the clinical and laboratory features; as the nephrotic syndrome may occur with any histological glomerulonephritis, and nephritic syndrome is the outcome of proliferative glomerulonephritis. So the ultimate diagnostic tool is renal biopsy and its light and fluorescent microscopy as well as ultrastructural study by electron microscope.

The interpretation of clinical features in the light of histological diagnosis of renal biopsy helps the clinician to detect any systemic disease associated with the renal disease (kidney disease). Majority of the patients with suspected glomerulonephritis need renal biopsy evaluation. However, in children with nephrotic syndrome; if there is no microscopic hematuria (blood in urine) and red cells' or granular casts, renal biopsy procedure may be avoided initially. In patients, who do not respond to steroid therapy; renal biopsy investigation is must. There are around one million glomeruli (1x10⁶ glomeruli) in each kidney and at least 5 glomeruli should be included in the renal biopsy evaluated histologically to achieve a diagnosis of glomerulonephritis.

Radiological and laboratory investigations in glomerulonephritis:

The clinical presentation, urine-analysis and microscopy findings, and presence of a normal upper & lower urinary tract on intravenous pyelography (IVP: a radiological investigation) or ultrasonography without any renal scarring could be indicative of glomerulonephritis, but there could be a need for renal biopsy.

Immune system associated investigations:

Our body is equipped with a multitasking immune system composed on lymphocytes, antibodies and complement system. The immune system always defends our body internally against a variety of infections and pathological conditions; and assessment of its components and abnormal products produced by it helps in diagnostic conclusions. Complement system of our body is composed of 9-components and boosts the body defense in association with cellular components. The blood level of complement components C3, C4 and C1q may be reduced or normal in some renal diseases. Low total serum complement, C3, C4 and C1q levels are observed in glomerulonephritis associated with circulatory immune complex disorders like systemic-lupus erythematosis (SLE), bacterial endocarditis and serum sickness. Normal levels of C4 and C1q but decreased level of C3 is generally observed in membranoproliferative glomerulonephritis (MPGN) and dense deposit disease of the kidney.

Following investigations are considered important to ascertain the diagnosis and type of glomerulonephritis:

Investigations for likely diagnosis of glomerulonephritis:

• Clinical presentation
• Urine analysis (proteinuria, hematuria and electrophoresis)
• Microscopy of urinary sediment
• Intravenous pyelography (IVP: Radiological investigation)
• Abdominal ultrasonography.

Investigations for likely type of glomerulonephritis:

• Estimation of serum complement components' level
• Detection of circulating immune complexes
• Detection of auto-antibodies such as anti-nuclear antibodies (ANA), anti-DNA antibodies and anti-glomerular basement membrane antibodies (anti-GBM antibodies)
• Renal biopsy

Investigations for assessing the implications of glomerulonephritis and monitoring the effect of therapy:

• Determination of 24 hour urinary protein
• Determination of level of serum proteins
• Determination of serum cholesterol and/or lipid profile
• Determination of serum creatinine, blood urea and serum electrolytes.

Therapy and Management of Glomerulonephritis

In my other articles you must have got ample information regarding classes or types of glomerulonephritis (GN). Primary glomerulonephritis accounts for about 30% patients requiring dialysis (a medical procedure of purifying blood with by passing through artificial kidney) and hospitalization. The yearly prevalence of primary GN is 0.002% that means 2 new patients per 100,000 population in a year. There are a variety of causes of primary GN with identical histopathological features. It is worth to mention here that there may be many immunopathological reasons in membranous glomerulonephritis (MGN). The character and severity of GN varies with the status of altered immune status of an individual. The understanding of pathogenesis of GN is must before initiating any therapy.

Regular follow-up in a clinic/renal clinic is must for the patient diagnosed of having a renal disease or glomerulonephritis. The follow-up provides an opportunity to the patient to learn about the complications of persistent GN and/or chronic renal failure. It has been observed that hypertension often develops coincidental with progression of renal disease. The hypertension needs to be kept under control in patients affected by persistent GN. The renal function deterioration causes edema in patients with glomerulonephritis. Though restriction in salt and water intake may cure the edema to some extent but diuretic drugs are preferred to treat the edema. Dietary management of progression of renal disease demands moderate reduction in protein intake (recommended: 0.8-1.0 g/kg body weight/day, during edema) to reduce the nephrotic overload and correction of proteinuria. Effective measures to reduce proteinuria are must to speed-up healing of renal lesions.

Corticosteroids, cyclophosphamide, chlorambucil and cyclosporin are the drugs of choice for the treatment of GN. About 95% of children generally respond to the first course of steroids within 8 weeks of commencement of treatment, whereas in adults it may take up-to 16 weeks and the percentage responding to the therapy could be around 80%. Oral prednisolone in single daily dose of 1mg/kg body weight is generally administered in adults. In children somewhat higher dose is required with reference to their body weights. Treatment of glomerulonephritis should never be tried as self help protocol as it needs regular follow-up. Parameters like body weight, blood pressure, 24 hour urinary protein, blood cells' count, blood urea and creatinine need to be worked out periodically to taper down the dose of steroids. Remission can also be achieved with cyclophosphamide, chlorambucil, cyclosporin and azathioprine. About 20-25% of patients are permanently cured with single course of treatment and around 50% may have relapse and need a repeat course of steroid treatment in combination with other immunosuppressive drugs. The dietary advice of nephrologist, controlled blood pressure and a treatment regimen for a sufficient time period may help a patient to keep a check on the complications of glomerulonephritis.

Nephrotic Syndrome and Associated Renal Lesions

Nephrotic syndrome may occur in any type of primary or secondary glomerulonephritis. Around two dozen histopathological categories or subcategories of glomerulonephritis are now recognized and etiological factors are largely determined. However, prevention and treatment of glomerulonephritis needs momentum to curb the development of irreversible renal failure. The main diagnostic feature of nephrotic syndrome is massive proteinuria (excretion of protein in urine) exceeding 3 g/24 hour. The other features of nephrotic syndrome, such as, hypoproteinemia (decreased level of proteins in blood), edema (swelling) and hyperlipidemia (elevated levels of lipids in blood) are consequential due to excretion of proteins in urine. Clinically the patient does not bother to consult a nephrologist or general physician until edema becomes evident. With the fall in the plasma osmotic pressure due to loss of the plasma proteins in urine the fluid from blood would leak into the interstitial space resulting in a reduction in circulating blood volume, but the kidneys try to maintain blood volume by retaining salts and water.

In children around 80% cases of nephrotic syndrome are due to minimal change disease(MCD) and in adults the dominance of MCD is lost. In adults the cause of nephrotic syndrome may be minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis or membranoproliferative glomerulonephritis (MPGN). Metabolic disorders like diabetes mellitus could also be a cause of nephrotic syndrome. Secondary amyloidosis is also known to cause renal lesions associated with nephrotic syndrome. Immunological disorders like systemic lupus erythematosis and vasculitis may also be a cause of glomerulonephritis. Renal biopsy evaluation by light microscopy (LM), immunofluorescence microscopy (IFM) and electron microscopy (EM) is must for an accurate diagnosis of type of glomerulonephritis in a patient of nephrotic syndrome. Minimal change disease, membranous glomerulonephritis (MGN), focal glomerulosclerosis, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN) and diffuse endocapillary glomerulonephritis are the common and primary causes of nephrotic syndrome. Focal segmental proliferative glomerulonephritis and diffuse proliferative glomerulonephritis with crescents are considered as uncommon-primary causes of nephrotic syndrome. Glomerulonephritis due to metabolic disorders, immunological disorders, toxemia of pregnancy or malignant conditions of kidney are labeled as secondary causes of nephrotic syndrome.

How Hypertension Is Related To Kidney

High blood pressure or hypertension is one of the most characteristic phenomenon of chronic glomerulonephritis. It is evident that renal lesions (pathological abnormality in kidney) of an ischemic kidney (kidney with poor blood supply) may cause hypertension. This has been seen in the secondary hypertension which develops in the course of glomerulonephritis. Mechanical as well as pathological compression of renal parenchyma has been found to cause hypertension in experimental animals. Chronic pyelonephritis may also cause hypertension.

A variety of renal disorders (kidney diseases) may give rise to hypertension. The kidney disease may be parenchymal or of vascular origin primarily. Morbid anatomical studies have revealed that partial occluding of even one of the renal arteries due to intimal thickening (thickening of internal lining of artery) could be a cause of hypertension due to renal involvement. The vascular or presser substance can be formed by an ischemic kidney. Healthy kidneys are capable of eliminating any presser substance formed in the system. The circulating presser substance is called hypertensin or angiotonin. The angiotonin is formed in the blood by the interaction of an enzyme, renin, secreted by ischemic kidney. The maintenance of normal blood pressure depends on a correct balance between the production of a presser material by the adrenal cortex and its removal by the kidneys. The hypertension may be the result of over-activity of the adrenal gland or some renal disorder.

The primary hypertension and the renal hypertension could be ruled out by the family physician of the patient. In the primary hypertension, the high blood pressure develops early without any renal insufficiency, but in glomerulonephritis, the hypertension develops gradually with renal insufficiency and anemia (fall in hemoglobin level in blood). However, if the patient is seen only after the development of uremia (high level of urea in blood) making distinction between the primary or secondary hypertension could be difficult.