Chronic Kidney Disease of Unknown Etiology (CKDu) Diagnostic Evaluation

Authored by Sourabh Sharma, published on 2026-11-12 13:45:50.0

Patient With CKD of Uncertain Etiology
- CKD Present for at Least 3 Months?
  - Evaluate for AKI or Acute Kidney Disease
  - Assess Diabetes, Hypertension, Systemic Features, Medications, Family History, and Urinary Symptoms
    - Document Occupational, Geographic, Heat, Dehydration, Pesticide, Water, and Nephrotoxic Exposures
      - Obtain Creatinine/eGFR, Urine Microscopy, UACR/UPCR, Electrolytes, Uric Acid, and Renal Ultrasound
        
        Established Alternative Etiology Confirmed?
        
        Classify as CKD With Established Alternative Etiology
        
        Select All Applicable Unexplained Clinical Phenotypes
        
        Order Targeted Autoimmune, Infectious, and Monoclonal Studies
        
        Credible Heavy-Metal or Toxic Exposure?
        
        Obtain Exposure-Specific Heavy-Metal or Toxicology Testing
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Obtain Genetic Evaluation for Hereditary Kidney Disease
        
        Credible Heavy-Metal or Toxic Exposure?
        
        Obtain Exposure-Specific Heavy-Metal or Toxicology Testing
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Define Structural Disease and Relieve Urinary Tract Obstruction
        
        Credible Heavy-Metal or Toxic Exposure?
        
        Obtain Exposure-Specific Heavy-Metal or Toxicology Testing
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Test for Glycosuria, Electrolyte Wasting, Acidification Defects, and Tubular Disease
        
        Exclude Drug-Induced, Infectious, Reflux, Obstructive, and Infiltrative Tubulointerstitial Disease
        
        Credible Heavy-Metal or Toxic Exposure?
        
        Obtain Exposure-Specific Heavy-Metal or Toxicology Testing
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Reassess Vascular, Metabolic, Drug-Related, and Other Identifiable Nephropathies
        
        Credible Heavy-Metal or Toxic Exposure?
        
        Obtain Exposure-Specific Heavy-Metal or Toxicology Testing
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Alternative Etiology Identified After Targeted Evaluation?
        
        Classify as CKD With Established Alternative Etiology
        
        Would Biopsy Clarify a Treatable or Alternative Etiology?
        
        Perform Kidney Biopsy If Procedurally Appropriate
        
        Biopsy Establishes an Alternative Etiology?
        
        Classify as CKD With Established Alternative Etiology
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
        
        Determine Exclusion Completeness and CKDu Phenotype Compatibility
        
        Classify as Probable CKDu
        
        Classify as Possible CKDu
        
        Do Not Classify as CKDu; Reassess Alternative Etiologies
CKDu Is a Diagnosis of Exclusion; No Single Biomarker or Exposure Is Diagnostic

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