Kidney-Function Decline and Kidney-Failure Endpoints

Definition and scope

Longitudinal renal outcomes based on explicitly defined kidney-function measurements, sustained changes, kidney replacement therapy, and/or death components, with confirmation and observation rules matched to the question. The target population, use, and analysis remain protocol decisions; this card explains the choices and their consequences rather than approving a study.

Operational specification

Record baseline and follow-up creatinine/eGFR dates, units, estimation equation/version, acute illness context, confirmation interval, sustained-decline rule, kidney-failure definition, replacement-therapy capture, and competing death. A diagnosis code for CKD stage is not interchangeable with a measured longitudinal eGFR change. Distinguish acute kidney injury, chronic decline, slope, and a composite kidney endpoint.

Analysis and diagnostics

Construct measurements using collection rather than note-signing dates, reconcile duplicate tests and equation changes, and assess differential testing. Confirm chronic/sustained changes under the protocol instead of treating every transient value as progression. For slope, model time and measurement frequency appropriately; for event endpoints, address interval ascertainment and competing events.

When NOT to use and common errors

Do not apply a single unsourced percentage threshold or confirmation interval to all renal studies, infer absence of decline from no testing, mix eGFR equations without assessment, or treat laboratory values measured after index as baseline confounders.

Worked example and implementation boundary

A synthetic patient has baseline eGFR 60 and a follow-up value 42 in the same units and equation. Calculate percentage decline; do not call it a confirmed endpoint without the protocol's confirmation evidence. The observed decline is 0.30, or 30%. A sustained clinical endpoint requires separately specified confirmation, context, and death handling. The code performs that explicitly stated calculation with synthetic inputs. It is not a complete fitted analysis and does not demonstrate the identification assumptions, estimate sampling uncertainty, or certify application in another population.

Data-source and reporting requirements

Preserve the provenance, dates, units, and observation rule for each input. Claims capture services and transactions under observable benefits; absence of a record is not proof that an event or resource use did not occur. EHR and registry measurements depend on the collection process and may miss care outside the system. Linked sources add reconciliation and selection questions. Primary collection can improve a missing domain but still requires valid measurement and follow-up. Report which of these limitations affects the stated use, which evidence supports the chosen inputs, and what remains uncertain.

Worked example

Scenario

A synthetic patient has baseline eGFR 60 and a follow-up value 42 in the same units and equation. Calculate percentage decline; do not call it a confirmed endpoint without the protocol's confirmation evidence.

Dataset

Synthetic inputs with units defined in the scenario; no patient data.

Steps

Result

The observed decline is 0.30, or 30%. A sustained clinical endpoint requires separately specified confirmation, context, and death handling.

Trade-offs

Code example

baseline_egfr = 60
followup_egfr = 42
result = (baseline_egfr-followup_egfr)/baseline_egfr
assert abs(result - 0.3) < 1e-9
print(result)

baseline_egfr <- 60
followup_egfr <- 42
result <- (baseline_egfr-followup_egfr)/baseline_egfr
stopifnot(abs(result - 0.3) < 1e-9)
print(result)

data worked_example;
  baseline_egfr = 60;
  followup_egfr = 42;
  result = (baseline_egfr-followup_egfr)/baseline_egfr;
  put result=;
run;

Citations

1. [1]Stevens PE, et al. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney International. 2024.
2. [2]U.S. Food and Drug Administration. Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments. Final guidance. October 2025.