Chronic Benign Tubular Albuminuria From Compound Heterozygous Variants in <i>CUBN</i> : A Case Report
Bibliographic record
Abstract
Rationale: Albuminuria is a commonly used parameter for predicting decline in kidney filtration function. Cubilin, encoded by CUBN, is a critical protein involved in protein reabsorption in the proximal tubule. Mutations in CUBN lead to Imerslund-Gräsbeck syndrome (IGS), a disorder characterized by vitamin B12 deficiency (and consequences related to that) with or without albuminuria. Recent evidence suggests that C-terminal variants in CUBN may lead to albuminuria without other features of IGS. Presenting concerns of the patient: Here, we report a case of a 52-year-old male with chronic, albumin-predominant, subnephrotic range proteinuria since his teenage years, but preserved estimated glomerular filtration rate (eGFR). Interventions: Neither angiotensin-converting enzyme (ACE) inhibition nor angiotensin Type II (AT-II) receptor blockade reduced his degree of albuminuria. Diagnosis: Genetic testing identified 3 distinct pathogenic variants in CUBN that were confirmed by segregation analysis to be a compound heterozygous mode of inheritance. All variants were downstream of the intrinsic factor-vitamin B12 binding domain of cubilin. The patient had normal vitamin B12 levels and did not exhibit any features of IGS. Outcomes: Kidney biopsy was not pursued for this patient as diagnostic clarification was achieved by non-invasive genetic testing alone. Novel findings: This case highlights several important lessons. First, not all albuminuria is made equal, and forms of tubular albuminuria can exist without compromising kidney filtration function. Second, identifying genetic forms of tubular albuminuria is key to avoiding ineffective interventions (eg, ACE inhibition, AT-II receptor blockade, sodium-glucose cotransporter-2 [SGLT2] inhibition) and unnecessary invasive procedures (eg, kidney biopsy). Third, the location of CUBN variants dictates phenotypic consequences, with C-terminal variants leading to albuminuria without vitamin B12 deficiency.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.003 | 0.002 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.006 | 0.004 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".