A 45-year-old man comes to the office for an annual medical visit. The patient has had prediabetes for the last 2 years. He feels well and takes no medications but has gained weight since his last visit a year ago. The patient has a strong family history of type 2 diabetes mellitus. Blood pressure is 124/78 mm Hg and BMI is 32 kg/m². Laboratory results show a fasting blood glucose of 157 mg/dL and serum creatinine of 0.7 mg/dL. Hemoglobin A1c is 7.4%. Urine assay shows no detectable albuminuria. Which of the following renal changes is most likely present in this patient at this time?

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11ec160b_3b53_9f15_9249_259e724dcd87_MD0001_00 This patient has type 2 diabetes mellitus, confirmed by elevated blood glucose and hemoglobin A1c. Diabetic nephropathy can occur with any form of diabetes mellitus and is the most common cause of end-stage renal disease in the United States. One of the earliest derangements that contributes to the pathogenesis of diabetic nephropathy is an increase in the filtered glucose load. This increases sodium resorption in the proximal tubule by the sodium glucose cotransporter, leading to decreased sodium and fluid delivery to the macula densa and subsequent activation of the tubuloglomerular autoregulation system. Subsequent dilation of the afferent arterioles and constriction of the efferent arterioles increases intraglomerular capillary pressure, resulting in an increased glomerular filtration rate (hyperfiltration) and glomerular hypertrophy (Choices B and C). Although the increased filtration rate appropriately counteracts the excessive sodium reabsorption and prevents fluid retention, over a prolonged period, chronically elevated intraglomerular capillary pressures contribute to glomerular structural changes. These include basement membrane thickening, mesangial expansion, and broadening of the podocyte foot processes, which result in the loss of small amounts of albumin in the urine (30-300 mg/day, or moderately increased albuminuria). Albuminuria is the earliest clinical sign of diabetic nephropathy and typically occurs before any appreciable rise in serum creatinine. Later in the disease process, there is widespread glomerulosclerosis and a decline in glomerular filtration. (Choice A) The increased glomerular hydrostatic pressure seen in diabetic nephropathy results in excess water loss in the glomerulus during filtration. The water loss leads to increased concentration of the plasma proteins and increased (rather than decreased) peritubular oncotic pressure. (Choice E) Increased oncotic pressure in Bowman's space occurs in diabetic nephropathy due to loss of albumin into the ultrafiltrate. However, this patient's urine assay shows no detectable albuminuria, so oncotic pressure would not be increased at this time. Educational objective: In diabetic nephropathy, early adaptive changes in the kidney cause a transient increase in glomerular filtration (hyperfiltration). As diabetic nephropathy progresses, glomerular filtration falls, with a concurrent increase in urine albumin loss. __________ References: Renal hyperfiltration related to diabetes mellitus and obesity in human disease. (http://www.ncbi.nlm.nih.gov/pubmed/22253940)

A 45-Year-Old Man Comes to the Office for an Annual