Case 09: The Diabetic Journey

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Session S3 · 2026-10-28 · in-session · 37 min Anchor: Proteinuria, hematuria and glomerular disease — nephrotic syndrome and edema from diabetic kidney disease, progressing to kidney failure · Integrates: CKD natural history and the pillars as GFR falls; nephrotic diuretics; diabetes pharmacology in CKD; anemia, mineral-bone disease and hyperkalemia as they appear; referral and KRT preparation; dialysis volume basics; the adult nephrotic differential at recognition level One-line hook: You will follow this patient for five years in your first job. The question at every visit is the same — is this still diabetes, and what do I keep, stop, start and hand off?

Author: Andrew Bland, MD, FACP, FAAP · Medical Associates Dept of Nephrology | UICOMP | UDPA | Butler COM

Learning Objectives

Answers for this section: Q1 · Q2 · Q3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12

1. Confirm that albuminuria is persistent (first-morning repeat, more than three months) before labelling a KDIGO A-category, and name the benign causes of transient and orthostatic proteinuria.
2. Start the kidney-protective pillars at eGFR 68 (ACE inhibitor titrated, SGLT2 inhibitor, statin) and accept a creatinine rise of up to 30 % at two weeks without stopping them.
3. Recognize nephrotic syndrome in a diabetic from the chart, list the clues that say it may not be diabetic kidney disease, order the adult secondary-cause screen and the anti-PLA2R antibody of membranous nephropathy, and stop the NSAID.
4. Dose an oral loop diuretic for nephrotic edema, adjust metformin, insulin, SGLT2 inhibitor and finerenone as eGFR falls, and treat a potassium of 5.5 before adding anything that raises it.
5. Prepare for kidney replacement therapy at G4 (education, vein preservation, fistula and pre-emptive transplant referral, conservative care named), and explain why dialysis starts for symptoms and why edema on hemodialysis is interdialytic gain; recognizing anemia and mineral-bone disease from first-line labs is discussed at Visit 3, not tested.

Warm-Up (individual commit before the case)

Answers for this section: Q1 · Q2 · Q3

Three readiness items. They test prerequisite knowledge only; no case grades reasoning from them.

Part 1 — Presentation

Answers for this section: Q4 · Q5

Visit 1 — the screening UACR

Dana Whitfield is a 49-year-old dental hygienist with type 2 diabetes for 16 years and hypertension for 8. Her last A1c was 8.4 %. Her last dilated eye exam was two years ago and was read as "normal"; she has not been back. Her mother had diabetes and died on dialysis. She does not smoke, walks the dog most evenings, and drinks a glass of wine on Fridays.

Two weeks ago she had a febrile upper respiratory infection (temperature 38.4 °C at an urgent care, where blood and urine were drawn that afternoon). She is well today and here for her routine diabetes visit. The urgent-care report is in her hand because it says "kidney protein high."

Vitals: BP 142/88 mmHg · HR 78 · T 36.8 °C · weight 92 kg · height 165 cm · BMI 33.8 kg/m² · no edema · fundi not examined (undilated).

Urgent-care labs (drawn the afternoon of the febrile illness):

Urinalysis (same afternoon sample): specific gravity 1.018, pH 5.5, protein 1+, glucose 2+, blood negative, leukocyte esterase negative, nitrite negative. Microscopy: 0–2 RBC/hpf, 0–2 WBC/hpf, no casts.

The arithmetic you should notice: BUN:creatinine is 16:1 (nothing prerenal), the anion gap is 139 − (104 + 25) = 10 (normal 8–12), and a creatinine of 1.01 in a 49-year-old woman gives an eGFR of 68 — CKD-EPI 2021, race-free. The glucose 2+ on the dipstick is what a serum glucose of 198 does; it is not a kidney finding.

Pause — commit before the reveal

What the confirmed A3 means, and what you start

The natural history of diabetic kidney disease runs in order: years of silent hyperfiltration, then albumin in the urine, then — often years later — a falling GFR. Albuminuria comes first. That is why every patient with type 2 diabetes gets a UACR and an eGFR every year, and why A3 moves the check to every six months.

Dana leaves Visit 1 with the kidney-protective "pillars" started at an eGFR of 68, not at 30:

• Lisinopril 10 → 20 mg daily today, with a plan to reach 40 mg by six weeks if potassium and blood pressure allow. An ACE inhibitor relaxes the small artery leaving the glomerulus, lowering pressure inside the filter — that is where its kidney protection lives.
• Empagliflozin 10 mg daily. An SGLT2 inhibitor blocks glucose and sodium reabsorption in the first part of the tubule; the extra sodium reaching the sensor at the macula densa tightens the artery entering the glomerulus. Same end — lower pressure inside the filter. Sick-day rule: hold it when she is vomiting, fasting or seriously ill. Counsel on genital yeast infections and hygiene. Lisinopril and the statin are justified today by her BP and LDL; empagliflozin is a reasonable glycemic add-on at an A1c of 8.4 and will be kidney protection once the A3 is confirmed.
• Atorvastatin 40 mg daily — high-intensity, as the ADA asks for a diabetic aged 40–75 with a risk factor; her LDL is 138 and her kidney is the risk factor.
• Metformin continues unchanged — eGFR 68 is well above every threshold.
• BMP in two weeks.

The two-week BMP: creatinine 1.21 mg/dL (up 20 % from 1.01), potassium 4.8 mEq/L, eGFR about 55. Blood pressure 132/80. No dizziness.

By six months: lisinopril 40 mg, BP 128/78, UACR 210 mg/g (A2 — albuminuria is the one target in kidney disease that still moves), eGFR 60, A1c 7.9 %.

Visit 2 — eighteen months later: "My legs and my face are swollen"

Dana is now 50. She has gained 9 kg in six weeks — a puffy face in the morning, shoes that do not fit by noon — and her urine has been "foamy, like beer" for two months. Two fasting glucose readings in the 60s led the covering PA to cut glargine from 36 to 28 units; Dana is pleased her sugars "finally look better." For her right knee she has taken two over-the-counter naproxen 220 mg tablets twice a day for four months — "I didn't think it counted." Five days ago the covering PA started furosemide 40 mg daily by phone; her weight is down 0.3 kg.

Vitals: BP 152/92 mmHg · HR 84 · T 36.9 °C · weight 101 kg (from 92) · SpO₂ 97 % on room air.

Exam: periorbital edema; 3+ pitting edema to both thighs and over the sacrum; decreased breath sounds at both bases; shifting dullness; no jugular venous distension; no S3; no rash, no synovitis.

Part 2 — Data

Answers for this section: Q6 · Q7 · Q8

Visit 2 labs

Urinalysis (first-morning, not during menses): specific gravity 1.020, pH 6.0, protein 4+ (>500 mg/dL), blood trace, glucose 3+, leukocyte esterase negative, nitrite negative. Microscopy: 3–5 RBC/hpf, round and uniform (isomorphic), no RBC casts, 0–2 WBC/hpf, oval fat bodies present, fatty casts with Maltese crosses under polarized light, occasional hyaline casts.

Renal ultrasound: right kidney 12.2 cm, left 12.0 cm, normal cortical echogenicity, no hydronephrosis. Chest radiograph: small bilateral pleural effusions. Echocardiogram (ordered for the effusions): ejection fraction 60 %, normal right ventricle, no pericardial effusion.

Check the numbers. Anion gap 137 − (105 + 24) = 8; add 2.5 for each 1 g/dL of albumin below 4 → corrected gap 13, upper-normal. BUN:creatinine 19:1 — mild, consistent with five days of diuretic. The calcium of 8.1 is a low-albumin artifact: corrected calcium = 8.1 + 0.8 × (4 − 2.1) = 9.6. The glucose 3+ on the dipstick is empagliflozin doing its job, not poor control — it will read 3+ for as long as she takes the drug.

Naming what you see

She meets every criterion of nephrotic syndrome: UPCR 7.8 g/g (nephrotic range is above 3.5), albumin 2.1 g/dL (below 3), edema to the thighs with effusions and ascites, and an LDL of 210 despite a statin. The sediment is bland except for lipid — the fat in the urine is the leaked lipoprotein being swept up by tubular cells. Trace blood with 3–5 round RBCs and no casts is not an active sediment; an active sediment is dysmorphic RBCs, acanthocytes (ring-shaped red cells with blebs — a glomerular bleeding sign), or RBC casts.

Why she is swollen, in plain words. Albumin is the protein that holds water inside blood vessels. When the filter leaks it into the urine faster than the liver can make it, water drifts out of the capillaries into the tissues — the underfill picture, and the one textbooks drew for decades. In most adults, though, the damaged kidney also hangs on to sodium directly at the far end of the tubule, so blood volume is normal or high — the overfill picture — and blood pressure runs up, as hers has. Either way the treatment is the same: get the sodium out with a loop diuretic and keep it out with a low-sodium diet. Albumin infusions are not routine; they leak out again within hours.

Why the LDL is 210 on a statin. A liver that is pouring out albumin to replace what is lost also pours out lipoproteins. Nephrotic hyperlipidemia is a feature of the syndrome, treated with a statin at full dose, and it resolves when the proteinuria does.

Pause — commit before the reveal

Pause — commit before the reveal

Visit 2 plan, written out: naproxen stopped — acetaminophen 650 mg every 8 hours as needed for the knee; furosemide 80 mg twice daily; sodium below 2 g/day with a dietitian visit; atorvastatin 80 mg; lisinopril 40 mg and empagliflozin continue; pneumococcal conjugate vaccine today; home weight log; BMP twice weekly; dilated eye exam this week; nephrology in one week; glargine stays at 28 units with hypoglycemia teaching — a nephrotic patient eats less and empagliflozin spills glucose, so her insulin need has genuinely fallen.

Part 3 — Course and Decisions

Answers for this section: Q9 · Q10 · Q11 · Q12

The nephrology visit — and the eye exam comes back

One week later Dana sees nephrology. The serologies are pending. The dilated eye exam from Tuesday is in the chart: no diabetic retinopathy.

The serologies return

ANA, C3 and C4, hepatitis B surface antigen, hepatitis C antibody, HIV, SPEP with serum free light chains, and anti-PLA2R all return normal or negative; the A1c is 7.6 %.

Nephrology's note, in plain words: DKD is plausible, but abrupt nephrotic syndrome and NSAID exposure leave a possible second glomerular disease. Discuss biopsy now. In this fictional course, after shared decision-making and review of bleeding risk, the team chooses a closely monitored interval off the NSAID, with an early clinical and laboratory review and a biopsy if recovery is inadequate or kidney function worsens. Deferral is an individual decision, not a rule based on bland sediment or negative serologies.

The subsequent course showed improvement but did not itself establish the histologic diagnosis. Eight weeks off naproxen, on lisinopril 40 mg, empagliflozin, furosemide 80 mg twice daily and a 2-g sodium diet, she weighs 93 kg and her UPCR is 4.1 g/g. At six months: UPCR 3.0 g/g, albumin 3.0 g/dL, edema gone, furosemide back to 40 mg twice daily, LDL 96 mg/dL on atorvastatin 80 mg.

The adult nephrotic differential at recognition level — minimal change disease, FSGS, membranous nephropathy and diabetic kidney disease, each with its typical patient, its chart clues and the student's first move — is reviewed in CBL-23 and CBL-24.

Three and a half years after Visit 1 — Visit 3

Dana is 52. Between visits her eGFR crossed 45 (metformin reduced to 500 mg twice daily) and then 41, at which point semaglutide was started and titrated to 1 mg weekly for an A1c of 7.8 % and her weight; glargine came down to 22 units. Then her eGFR fell faster than nephrology had expected — 58 to the low 30s by year three — so a kidney biopsy was done: advanced diabetic glomerulosclerosis, no second disease; the pillars continued. Today she is tired, her legs swell by evening, and she gets calf cramps at night. Since she was told to cut sodium she has been using a potassium-chloride salt substitute "so food tastes like something."

Vitals: BP 138/84 mmHg · HR 76 · weight 90 kg · 1+ ankle edema · lungs clear · no rub.

Arithmetic first. Anion gap 138 − (107 + 19) = 12; albumin-corrected 14 — the mild retention acidosis of G4 (the kidney can no longer excrete the day's acid). BUN:creatinine 17:1. Creatinine 2.7 in a 52-year-old woman is an eGFR of 21: G4, A3. Potassium 5.5 with a normal ECG — the 5.1–5.9 band, where the ECG is usually normal and calcium is not indicated.

Four new problems have arrived together, and each has a first-line answer a student should own:

• Hyperkalemia. Stop the potassium-chloride salt substitute, review drugs and dietary contributors, and treat according to potassium trend, clinical state and kidney function. A binder may help preserve indicated RAAS treatment. Repeat potassium within48–72hours at this newly identified5.5, sooner if the clinical state or trajectory worsens. A normal ECG does not establish safety; uncontrolled hyperkalemia may require treatment adjustment.
• Anemia of CKD. Less erythropoietin and iron the body cannot use well. Screen with a hemoglobin at least yearly in G3 and twice yearly in G4–G5; order ferritin and TSAT and rule out the other causes (B12, folate, bleeding — she has none). Ferritin 80 and TSAT 15 % mean iron first, oral or intravenous (an oral trial of 1–3 months is reasonable in non-dialysis CKD; nephrology may choose IV). An erythropoiesis-stimulating agent is nephrology's decision, started only after iron is replete, with a hemoglobin target below 11.5 g/dL because higher targets cause stroke and clots.
• CKD-mineral and bone disease. The failing kidney retains phosphorus, makes less active vitamin D, and the parathyroid glands respond by making more PTH, which pulls calcium and phosphorus out of bone. At G4: calcium and phosphorus every 3–6 months, PTH every 6–12 months, 25-OH vitamin D. First moves: dietary phosphorus — the additives in processed food first — with the dietitian; cholecalciferol 2,000 IU daily for a 25-OH D of 18; watch the PTH trend. If phosphorus stays up, a phosphate binder — calcium-based or non-calcium — chosen by nephrology. Active vitamin D and calcimimetics are nephrology's.
• Metabolic acidosis. Confirm persistent bicarbonate 19 and assess the acid-base state. KDIGO 2024 individualizes treatment, with <18 mmol/L as an example of clinically important acidosis. In this fictional course nephrology chooses a monitored sodium bicarbonate trial for acid-base control; benefit for slowing progression is uncertain. Follow blood pressure, volume, potassium and bicarbonate.

And one old problem: BP 138/84 is above the <130/80 goal for CKD — amlodipine goes to 10 mg today (lisinopril is already maximal).

And the diabetes is "better." Glucose 118, A1c 6.9 — the chart looks like success. It is not. The kidney clears about a third of the body's insulin and makes new glucose when she fasts; as it fails, injected insulin lasts longer and the fasting floor drops. Her appetite is falling. And the A1c is unreliable in advanced CKD — shortened red-cell survival and ESAs read it low, iron deficiency reads it high — so her glucose log and sensor, not the A1c, decide the next dose. Glargine comes down to 18 units today. Hypoglycemia is the diabetic complication that arrives at G4.

Pause — commit before the reveal

Five years after Visit 1 — Visit 4

Dana is 54. She is nauseated most mornings, itches at night, says food "tastes like a penny," and has lost 4 kg because she is not hungry. She is sleeping badly. No chest pain, no breathlessness at rest, no confusion. A left brachiocephalic fistula was created five months ago and vascular surgery cleared it for use two weeks ago; it has a good thrill and bruit. She is on the transplant list, and her sister's evaluation is under way.

Vitals: BP 148/86 mmHg · HR 80 · weight 86 kg · SpO₂ 97 % · pale · 1+ ankle edema · lungs clear · no pericardial rub · no asterixis.

The four drugs that change at this visit:

Unchanged or nephrology-managed since Visit 3: atorvastatin 80 mg, amlodipine 10 mg, semaglutide 1 mg weekly, patiromer 8.4 g daily (the binder that lets the ACE inhibitor stay), a non-calcium phosphate binder with meals, sodium bicarbonate 650 mg twice daily, cholecalciferol 2,000 IU daily, and darbepoetin every two weeks after intravenous iron.

Anion gap 136 − (104 + 17) = 15, albumin-corrected 16 — the acidosis of G5. BUN:creatinine 17:1. Creatinine 5.3 in a 54-year-old woman is an eGFR of 9.

The dialysis decision is made by her symptoms, not by the 9. Run the emergencies first — the AEIOU list, each of which is a same-day call to nephrology: Acidosis that is severe and refractory (hers is 17, treated, not that); Electrolytes — refractory hyperkalemia with ECG changes (5.3 on a binder with a normal ECG is not that); Ingestion of a dialyzable toxin (no); Overload — pulmonary edema unresponsive to diuretics (lungs clear); Uremia with pericarditis, encephalopathy or bleeding (no rub, no confusion, no bleeding). None present. What she does have is the ordinary uremic syndrome: anorexia, nausea, pruritus, dysgeusia, weight loss, fatigue, poor sleep — and that, with an eGFR under 10 and every medical lever already pulled, is the elective indication. The IDEAL trial randomized people to start dialysis "early" at an eGFR of 10–14 or "late" when symptoms demanded it (planned eGFR 5–7, though most started earlier for symptoms — mean 9.8) and found no difference in survival, hospitalization or quality of life; the late group simply spent less of their lives on a machine. So she starts in-center hemodialysis next week through the fistula she has been protecting for eighteen months, with a plan to move to home dialysis or transplant. Empagliflozin stops at dialysis start. Glargine comes down to 8 units. Furosemide continues — she still makes urine. Lisinopril continues for now.

The first month on hemodialysis

The unit sets her dry weight — the weight at which she leaves dialysis neither swollen nor cramping and faint — at 84 kg. On the first Monday of her second month she arrives at 88 kg, 4 kg above dry weight, with 2+ edema to the knees, breathless on the stairs, BP 162/92. Her gain from Friday's treatment to Monday was 4 kg. She still makes about 600 mL of urine a day. Her food diary shows deli meat, canned soup and a salted-pretzel habit — about 4 g of sodium a day.

Resolution and Teaching Points

Answers for this section: Q1 · Q2 · Q3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12

Six months into dialysis Dana's dry weight is 83 kg and her gains run under 2 kg. The edema is gone. The itching eased when her phosphorus came under 5.5. Her hemoglobin is 10.8 g/dL on iron and a modest ESA dose. She works four days a week. Her sister was cleared as a living donor, and a transplant is scheduled — not pre-emptive, which was the goal, but eleven months after her first treatment, which is a very good outcome. The question at each of her four visits was the same — is this still diabetes, and what do I keep, stop, start and hand off? — and at each one the answer was found by checking the chart against a short list, not by guessing.

Clinical Pearl — Albuminuria first, GFR later Albuminuria can precede GFR decline, as in this case, but nonalbuminuric DKD also occurs. Screen with both UACR and eGFR. Confirm persistent abnormalities and exclude transient causes before applying a chronic diagnosis; a first-morning sample improves confirmation but is not the only valid specimen.

Clinical Pearl — Start the pillars at 68, not 30, and accept the dip ACE inhibitor titrated to full dose, SGLT2 inhibitor started at any eGFR of 20 or above, statin. Both kidney drugs lower pressure inside the glomerulus, so creatinine rises 10–30 % and then plateaus — that rise may be hemodynamic, and must be interpreted with potassium, perfusion and the trend. Recheck at two weeks; continue. As GFR falls: SGLT2 inhibitor continues to dialysis; finerenone waits for a potassium of 5.0 or below; metformin reduces below 45 and stops below 30; insulin requirements fall and the A1c lies.

Clinical Pearl — A diabetic's nephrotic syndrome is diabetes until the clues say otherwise Sudden nephrotic onset, short diabetes duration, hematuria or an active sediment, no retinopathy, rapid GFR decline, positive serologies — any of these earns the adult secondary-cause screen (A1c, HIV, hepatitis B and C, ANA with C3/C4, SPEP and free light chains, anti-PLA2R when membranous nephropathy is suspected) and a referral. Stop the NSAID: it causes minimal change disease and membranous nephropathy as well as interstitial nephritis. Biopsy is nephrology's decision, made after the serologies and the contraindications.

Clinical Pearl — Nephrotic diuretics are oral, bigger, and twice a day In this stable outpatient, increasing loop dose and frequency with sodium restriction is reasonable. Poor absorption or refractory edema may require IV treatment; oral therapy is not a universal rule. Individualize weight-loss goals and monitor blood pressure, kidney function and electrolytes. Add-on diuretics and prophylactic anticoagulation require an individualized risk assessment.

Clinical Pearl — Prepare at G4; start dialysis for symptoms KDIGO 2024 uses 2-year kidney-failure risk >10% to help plan multidisciplinary care and >40% to help time modality education and preparation. Choose transplantation, dialysis modality, access or conservative care with the patient; fistula referral is not automatic for every person. Preserve vessels in both arms and obtain access-team advice before a PICC. Start dialysis from the composite clinical picture, not eGFR alone; tailor ultrafiltration to tolerance and continue a loop only while useful.

Pitfall — Stopping the drugs that protect the kidney Avoid stopping protective treatment solely for a modest stable hemodynamic creatinine rise. Manage reversible hyperkalemia where possible, but adjust treatment if potassium remains uncontrolled or acute illness intervenes. A normal ECG cannot establish potassium safety. Continue an established SGLT2 inhibitor below its initiation threshold when tolerated, with sick-day precautions.

Pitfall — The PICC line in the fistula arm A G4 patient who "needs IV iron" gets a PICC, the upper-arm vein it was threaded through scars and the central vein stenoses, and two years later there is no fistula — she starts dialysis through a catheter in her neck with the infection and mortality that come with it. Vein preservation is a standing order from the day the KFRE is high, written in the chart and on the patient's wristband.

Concept Links

Answers for this section: Q1 · Q2 · Q3 · Q4 · Q5 · Q6 · Q7 · Q8 · Q9 · Q10 · Q11 · Q12

Assigned reading: the explanations in this case and the question-linked course evidence guide. The objective map distinguishes tested decisions from concepts taught in explanations.

Concepts: ckd-06, ckd-09, ckd-12, ckd-13, ckd-17, ckd-21, ckd-22, ckd-23, ckd-24, ckd-25, glom-04, glom-05, glom-07, glom-10, glom-11, glom-18, glom-19, glom-20, glom-21, glom-22, glom-23, glom-24, structural-23, structural-26.