A 44-year-old man presents for a checkup. The patient says he has to urinate quite frequently but denies any dysuria or pain on urination. Past medical history is significant for diabetes mellitus type 2 and hypertension, both managed medically, as well as a chronic mild cough for the past several years. Current medications are metformin, aspirin, rosuvastatin, captopril, and furosemide. His vital signs are an irregular pulse of 74/min, a respiratory rate of 14/min, a blood pressure of 130/80 mm Hg, and a temperature of 36.7°C (98.0°F). His BMI is 32 kg/m2. On physical examination, there are visible jugular pulsations present in the neck bilaterally. Laboratory findings are significant for the following: Glycated Hemoglobin (Hb A1c) 7.5% Fasting Blood Glucose 120 mg/dL Serum Electrolytes Sodium 138 mEq/L Potassium 3.9 mEq/L Chloride 101 mEq/L Serum Creatinine 1.3 mg/dL Blood Urea Nitrogen 18 mg/dL Which of the following is the next best step in the management of this patient?

Replace captopril with valsartan.

A 67-year-old man presents to his primary care provider because of fatigue and loss of appetite. He is also concerned that his legs are swollen below the knee. He has had type 2 diabetes for 35 years, for which he takes metformin and glyburide. Today his temperature is 36.5°C (97.7°F), the blood pressure is 165/82 mm Hg, and the pulse is 88/min. Presence of which of the following would make diabetic kidney disease less likely in this patient?

Normal-to-large kidneys on ultrasound

Gradual reduction of glomerular filtration rate (GFR)

A 51-year-old African American man presents to his primary care physician’s office for an annual visit. He has no major concerns and says that he has been healthy for the last year. His past medical history is significant for diabetes as well as long standing hypertension that has developed gradually since his 30's; however, he has refused to take any medications. Physical exam shows no abnormal findings. Routine laboratory testing reveals the following: Serum creatinine concentration: 1.5 mg/dL Blood urea nitrogen: 31 mg/dL Based on these results, urine studies are conducted that reveal mild proteinuria of less than 1 g/day and no casts. Which of the following is most likely associated with the cause of this patient's elevated creatinine?

Apple-green birefringent lesions

A 55-year-old Caucasian woman visits her family physician for a checkup and to discuss her laboratory results from a previous visit. The medical history is significant for obesity, hypothyroidism, and chronic venous insufficiency. The medications include thyroxine and a multivitamin. In her previous visit, she complained about being hungry all the time, urinating multiple times a day, and craving water for most of the day. Blood and urine samples were obtained. Today her blood pressure is 120/70 mm Hg, the pulse is 80/min, the respiratory rate is 18/min, and the body temperature is 36.4°C (97.5°F). The physical examination reveals clear lungs with regular heart sounds and no abdominal tenderness. There is mild pitting edema of the bilateral lower extremities. The laboratory results are as follows: Elevated SCr for an eGFR of 60 mL/min/1.73 m² Spot urine albumin-to-creatinine ratio 250 mg/g Urinalysis Specific gravity 1.070 Proteins (++) Glucose (+++) Nitrites (-) Microscopy Red blood cells none White blood cells none Hyaline casts few A bedside renal ultrasound revealed enlarged kidneys bilaterally without hydronephrosis. Which of the following kidney-related test should be ordered next?

No further renal tests are required

A 75-year-old man presents to his primary care physician for foot pain. The patient states that he has had chronic foot pain, which has finally caused him to come and see the doctor. The patient's past medical history is unknown and he has not seen a doctor in over 50 years. The patient states he has led a healthy lifestyle, consumes a plant-based diet, exercised regularly, and avoided smoking, thus his lack of checkups with a physician. The patient lives alone as his wife died recently. His temperature is 98.1°F (36.7°C), blood pressure is 128/64 mmHg, pulse is 80/min, respirations are 13/min, and oxygen saturation is 98% on room air. The patient's BMI is 19 kg/m^2 and he appears healthy. Physical exam demonstrates a right foot that is diffusely swollen, mildly tender, and deformed. The patient's gait is abnormal. Which of the following is associated with the underlying cause of this patient's presentation?

Hyperfiltration damage of the kidney

Methicillin-resistant bacterial agent

Diabetic nephropathy for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

Pathophysiology - The Sugar Siege

Chronic hyperglycemia drives glomerular damage via two main pathways:
- Non-enzymatic Glycation: Glucose binds to proteins, forming Advanced Glycation End-products (AGEs).
- PKC Activation: Hyperglycemia activates the Protein Kinase C (PKC) pathway.
These pathways trigger a cascade leading to structural and functional kidney changes.

Histopathology of Diabetic Nephropathy

⭐ The earliest detectable change in diabetic nephropathy is glomerular hyperfiltration, where the GFR is paradoxically increased.

Diagnosis & Staging - Finding the Leaks

Annual Screening:
- Type 2 DM: Start at diagnosis.
- Type 1 DM: Start 5 years post-diagnosis.
Primary Test: Urine Albumin-to-Creatinine Ratio (UACR) from a spot sample.
- Confirm with 2 positive tests over 3-6 months.
Staging Albuminuria (UACR):
- A1 (Normal): < 30 mg/g
- A2 (Microalbuminuria): 30-300 mg/g
- A3 (Macroalbuminuria): > 300 mg/g
Monitor eGFR: Track decline to stage CKD (G1-G5).

KDIGO 2012 CKD Prognosis by GFR and Albuminuria

⭐ Diabetic retinopathy is strongly associated with nephropathy; its presence supports the diagnosis, while its absence in a proteinuric T1DM patient may suggest another cause.

Management - The Damage Control Plan

Primary Goals:
- Glycemic Control: Target HbA1c ~7%.
- BP Control: Target <130/80 mmHg.
- RAAS Blockade: For albuminuria (UACR >30 mg/g).
  - - Start ACE Inhibitor (-pril) or ARB (-sartan).
  - - ⚠️ Monitor for hyperkalemia.
Cardio-Renal Protection:
- SGLT-2 Inhibitors (-gliflozin): Standard of care for CKD with albuminuria. Reduces intraglomerular pressure.
- Finerenone: Non-steroidal MRA; reduces fibrosis and inflammation.

⭐ SGLT-2 inhibitors slow eGFR decline and reduce risk of cardiovascular events, benefits that are independent of their glucose-lowering effects.

High‑Yield Points - ⚡ Biggest Takeaways

Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States.

The earliest clinical sign is microalbuminuria; screen annually with a urine albumin-to-creatinine ratio (UACR).

ACE inhibitors or ARBs are the first-line treatment to slow disease progression, even in normotensive patients.

Kimmelstiel-Wilson lesions (nodular glomerulosclerosis) are pathognomonic histological findings.

Strict glycemic control (target HbA1c < 7%) and aggressive blood pressure control (< 130/80 mmHg) are paramount.

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Diabetic nephropathy