Discuss the clinical and laboratory findings along with the gross and microscopic pathologic appearances of renal disease in patients with diabetes mellitus. (<300 words)

Diabetes mellitus typically causes glucosuria as detected on urinalysis. This leads to the typical clinical findings of polyuria and polydipsia. Progressive renal disease can further lead to renal failure with increasing BUN and creatinine as measured in serum. Renal failure also leads to decreased renal concentrating ability. The condition of diabetic ketoacidosis is manifested by the finding of ketone bodies in urinalysis.

Diabetics are more prone to infection, and this can results in acute pyelonephritis characterized by patchy tubulointerstitial infiltrates of neutrophils and increased white blood cells and white blood cell casts on urinalysis. Grossly, small abscesses or yellow-tan infiltrates can appear. Multiple episodes of acute pyelonephritis can result in chronic pyelonephritis which eventually lead to loss of renal function through scarring and loss of parenchyma. An uncommon but severe complication of uncontrolled diabetes mellitus is renal papillary necrosis which could be manifested by significant hematuria.

Renal damage from diabetes mellitus may occur because of vascular disease with thickening of large arteries and arterioles which appears as arterial and/or arteriolar nephrosclerosis,. Nephrosclerosis can lead to hypertension. Lesions more specific to diabetes include diffuse and nodular glomerulosclerosis (Kimmelstiel-Wilson lesion). These lesions occur when the mesangial matrix is increased either diffusely throughout the glomerulus or as nodular masses in the glomerular periphery and glomerular capillary basement membranes are thickened. All of the above lesions are slowly progressive over decades, leading to progressive loss of renal function. This can be evidenced on urinalysis by finding proteinuria, sometimes in the nephrotic range. The final result of diabetic renal disease is end-stage renal disease. This is characterized by small, shrunken kidneys with extensive cortical scarring.

Discuss the pathologic and clinical features of acute tubular necrosis. (<250 words)

Acute tubular necrosis (ATN) is the most common cause of acute renal failure often due to ischemia with decreased renal blood flow, usually from cardiac failure. The proximal tubular cells are most sensitive to ischemic injury, and there is segmental necrosis. The epithelium becomes flattened and the tubules dilated.

Immune complexes can damage the tubular epithelium, as in systemic lupus erythematosus (SLE). A positive antinuclear antibody test helps diagnose SLE. A special form of immunologic injury occurs when methicillin binds to the basement membrane, acting as a hapten and resulting in tubular injury.

The cell-mediated injury of acute renal allograft rejection occurs when both CD4 and CD8 lymphocytes accumulate, releasing cytokines that mediate an inflammatory response that damages renal tubules. A history of transplantation with immunosuppressive therapy would help to diagnose this condition.

ATN can occur from chemical injury. Sometimes drugs such as aminoglycoside antibiotics, sulfa compounds, or cyclosporine are implicated. Ingestion of toxins such as ethylene glycol, lead, or mercury can produce tubular injury. Radiocontrast dyes and myoglobinuria can also produce tubular injury. Though the proximal tubular necrosis can be extensive, basement membranes tend to be spared.

Patients with ATN initially become oliguric and have increasing BUN with decreased urine concentrating ability. Broad casts and sloughed renal tubular epithelial cells can appear in the urine. If the injury is not too severe and the underlying condition is treated or removed, the tubular epithelium can regenerate. During the healing phase, the patient can have polyuria.

Discuss clinical, laboratory, and pathologic findings in the workup of a patient with nephrotic syndrome. (<250 words)

Nephrotic syndrome is defined as the loss of more than 3.5 g/day of protein in the urine. This results in laboratory findings of hypoalbuminemia, hyperlipidemia, and lipiduria. The patients may have findings ranging from lethargy to hypertension. Most have edema. There are a variety of etiologies, most of them resulting from glomerular damage.

The most common cause of nephrotic syndrome in children is minimal change disease. By light microscopy, the glomeruli appear normal. However, by electron microscopy there is fusion of epithelial cell foot processes. No immune deposits are seen. The proteinuria is very selective. Lipiduria may lead to the finding of oval fat bodies on urinalysis. Most patients respond to steroids.

Membranous glomerulonephritis is the most common adult cause for nephrotic syndrome. It is characterized by a granular deposition of immune complexes -- mostly IgG and C3 -- in the glomerular capillary loops, leading to thickening of the glomerular basement membrane and the apperance of "spikes" by silver staining. In a few of these cases, the patient has viral hepatitis or an underlying cancer.

Also seen in both adults and children is focal segmental glomerulosclerosis in which some glomeruli show focal scarring. The response of FSGS to steroids is poor, and half of these patients go on to end-stage renal disease. In membranoproliferative glomerulonephritis, there is mesangial proliferation with immune complex deposition. In type I MPGN there is deposition of IgG and C3 with splitting of the glomerular basement membrane. In type II there are dense deposits of deposits of C3 and the patients often have C3 nephritic factor.

Systemic diseases in adults that may be associated with nephrotic syndrome include diabetes mellitus with diabetic nephropathy, systemic lupus erythematosus, and amyloidosis.