A group of autosomal dominant tubulointerstitial nephropathies characterized by slowly progressive chronic kidney disease with a bland urinary sediment (little blood/protein), normal-to-small kidneys (± few late medullary/corticomedullary cysts), and histology showing tubular atrophy and interstitial fibrosis. Modern nomenclature groups these conditions as ADTKD, subclassified by gene (most often UMOD, MUC1, REN, HNF1B; rarer SEC61A1, DNAJB11, APOA4). “Medullary cystic kidney disease (MCKD)” (types 1 & 2) corresponds largely to ADTKD‑MUC1 and ADTKD‑UMOD, and is a misnomer because cysts are not required for diagnosis.
Often mislabeled as “CKD of unknown cause,” ADTKD leads to ESRD in mid‑to‑late adulthood (median ~40s–50s depending on subtype) and is under‑recognized on exams and in clinic. Early recognition guides family screening, avoids unnecessary workups/biopsies, explains early gout (UMOD/REN), and prompts appropriate counseling (excellent transplant outcomes; disease usually does not recur in the graft).
Common thread:autosomal‑dominant family history of CKD across generations, minimal proteinuria, bland urine, slowly rising creatinine beginning in the teens–30s.
ADTKD‑UMOD (formerly MCKD2/FJHN):hyperuricemia with early gout (often teens/20s), impaired urinary concentration (polyuria/nocturia), normal‑to‑small kidneys with few cysts; CKD progression over decades.
ADTKD‑MUC1 (formerly MCKD1): isolated kidney disease—no consistent extrarenal features; bland urine, CKD beginning in late teens/20s; cysts may be absent or few; many standard sequencing panels miss MUC1 (specialized testing needed).
ADTKD‑REN: childhood presentation with hypotension, anemia, mild hyperkalemia & metabolic acidosis, salt craving/polyuria; later hyperuricemia ± gout; AD family history.
ADTKD‑HNF1B (RCAD):kidney disease with renal cysts/dysplasia plus MODY5 diabetes, hypomagnesemia, and GU/pancreatic/hepatic anomalies; variable course.
When to suspect ADTKD: AD family history of CKD + bland urine (protein <~500 mg/day) + normal/small kidneys (± few medullary/corticomedullary cysts).
First steps: urinalysis (often bland), serum uric acid (high in UMOD/REN), renal ultrasound (often normal early; later small kidneys ± few cysts).
Genetic testing: order an inherited kidney disease panel including UMOD, MUC1, REN, HNF1B. Note: MUC1 frameshift variants are hard to detect with routine NGS/Sanger; targeted assays or immunostaining for MUC1fs may be required at specialized labs.
Biopsy? Not diagnostic alone (nonspecific tubulointerstitial fibrosis/TA, thickened/lamellated TBM; microcysts). Use it mainly to exclude other etiologies.
Subtype clues: early gout → UMOD/REN; childhood anemia/hyperkalemia/hypotension → REN; extrarenal features (MODY5, GU malformations, low Mg) → HNF1B; isolated CKD with negative routine panels → MUC1.
History of drug exposure; may have sterile pyuria, WBC casts; no autosomal‑dominant pattern.
No disease‑modifying therapy yet—CKD care (BP control, RAAS blockade as tolerated, avoid nephrotoxins, treat acidosis, manage anemia/mineral bone disease).
Gout/hyperuricemia (UMOD/REN/HNF1B):allopurinol or febuxostat for flares/prevention; discuss risks (hypersensitivity; pregnancy considerations). Avoid meds that raise urate (e.g., high‑dose thiazides) when possible.
ADTKD‑REN: consider fludrocortisone and liberal salt intake to address hypotension/hyperkalemia; treat childhood anemia per CKD practice (± EPO).
HNF1B (RCAD): manage MODY5 diabetes, monitor/treat hypomagnesemia and other extrarenal issues.
Transplantation: excellent outcomes; recurrence in the allograft is not expected for UMOD/MUC1/REN subtypes.
MCKD is a misnomer—you can have ADTKD without visible cysts; kidneys are often normal or small, not massively cystic (contrast with ADPKD).
Urine is boringly bland (little protein/hematuria) despite worsening CKD—this is a classic exam clue.
Transplant works well—disease typically does not recur in the graft.
Early‑onset gout (teens/20s) with a family history of CKD → think ADTKD‑UMOD.
Child with CKD + anemia + mild hyperkalemia + low BP in a dominant pedigree → concerning for ADTKD‑REN.
“CKD of unknown cause” with bland urine and normal/small kidneys across generations—do not miss ADTKD; refer for genetic testing.
Suspect inherited tubulointerstitial disease → confirm AD family history and bland urine (low protein/hematuria).
Renal ultrasound → normal/smallkidneys ± few medullary/corticomedullary cysts.
Order genetic testing panel (UMOD, MUC1, REN, HNF1B; add SEC61A1/DNAJB11 if available). If panel negative but suspicion high → arrange MUC1‑specific testing.
Manage per CKD guidelines; treat gout; fludrocortisone for ADTKD‑REN hypotension/hyperkalemia. Consider transplant when advanced.
Teen with recurrent gout and a father/uncle on dialysis; UA with trace/no protein, ultrasound shows small kidneys with few or no cysts → ADTKD‑UMOD.
Child with fatigue, anemia, mild hyperkalemia, low‑normal BP, polyuria; parent with CKD in 30s–40s → ADTKD‑REN.
Adult with CKD stage 3, bland urine, normal‑size kidneys (no significant cyst burden), negative UMOD/HNF1B/REN on panel; specialized testing confirms MUC1 frameshift → ADTKD‑MUC1.
Don’t confuse with ADPKD: huge cystic kidneys, numerous cysts, higher proteinuria; or medullary sponge kidney: nephrocalcinosis, stones, often normal kidney function.
Case 1
A 22‑year‑old man has recurrent podagra and a father who started dialysis at 48.
Case 2
A 7‑year‑old boy has fatigue, **anemia**, mild **hyperkalemia**, low‑normal BP, nocturia, and a mother with CKD.
Case 3
A 35‑year‑old woman with slowly rising creatinine since age 24; urine is bland; imaging shows normal‑sized kidneys without many cysts. Her father required transplant at 52.
Public‑domain Gray’s Anatomy diagram of a nephron (tubules and collecting system in cortex/medulla), the compartment affected in ADTKD.
