Dipstick Proteinuria Screening of Asymptomatic Adults to Prevent Progressive Renal Disease

Prepared by Ryuta Nagai, MD, FRCPC, Research Associate, Department of Preventive Medicine and Biostatistics, Elaine E.L. Wang, MD, FRCPC, Associate Professor of Pediatrics and of Preventive Medicine and Biostatistics, and William Feldman, MD, FRCPC, Professor of Pediatrics and of Preventive Medicine and Biostatistics, University of Toronto, Ontario



Objective
To make recommendations regarding dipstick proteinuria screening of asymptomatic adults in Canada to prevent endstage renal disease (ESRD).

Burden of Suffering
Over 13,000 patients are on ESRD programs (dialysis and transplantation) in Canada. An additional 2,000 patients enter dialysis programs every year, an annual increase of 7%. The cost of health care incurred through dialysis and transplantation is enormous. The average cost of peritoneal or hemodialysis is $50-58,000 per patient year with lower figures for long-term successful renal allografts. By comparison, the cost of a urine dipstick analysis is approximately 30 cents per test which translates to $7 million if all adults were to be screened in Canada. These fiscal calculations, however, do not take into consideration the diminished quality of life associated with long-term dialysis.

Options
To conduct or not conduct dipstick proteinuria screening of all asymptomatic adults.

Outcomes
Dipstick test properties included sensitivity, specificity and positive predictive value. Indicators of the effectiveness of renal therapies were renal mortality, patient mortality and rate of progression to ERSD. Costs of dipstick testing were compared with those related to treatment of ESRD.

Evidence
MEDLINE was searched for 1966 to December 1992 using the keywords "evaluation studies", "proteinuria", "population studies", "prospective studies", "screening", "protein restriction", "hypertension", "kidney disease", "antihypertensive agents", "diabetes mellitus" and "diabetic nephropathy". Study results were synthesized in table or graph format only.

Values
The 13-member Task Force of experts in family medicine, geriatric medicine, pediatrics, psychiatry and epidemiology used an evidence-based method for evaluating the effectiveness of preventive health care interventions. Recommendations were not based on cost-effectiveness of options. Patient preferences were not discussed.

Background papers providing critical appraisal of the evidence and tentative recommendations prepared by the chapter author were pre-circulated to the members. Evidence for this topic was presented and deliberated upon in 1- to 2-day meetings, 2 to 3 times per year from January 1993 to June 1993. Consensus was reached on final recommendations.

Benefits, Harms, and Costs
Dipstick urine tests are simple, non-invasive tests, usually involving a pH-dependent tetrabromphenol-blue indicator system. Sensitivity and specificity range from 95% to 99%. A review of 11 studies found an overall positive predictive value of 30%, ranging from 6% to 70%, depending on the population under study. (A positive test result was defined as ³ 0.3 g/L, and all patients with persistent non-orthostatic proteinuria were designated as having "possibly significant renal disease", in order to give an overestimate of those at risk for ESRD.)

There is no effective nontoxic therapy to treat most renal diseases detected with dipstick testing. Uncontrolled trials suggest some benefit of blood pressure control in patients with mild to moderate hypertension associated with chronic renal failure, but this has not been demonstrated in a prospective controlled trial. Data from large hypertension RCTs looking at cardiovascular mortality found no differences in renal mortality in patients with better blood pressure control. There is good evidence from an RCT that moderate restriction of dietary protein slows the rate of ERSD progression, but safety and long-term compliance are unknown.

An RCT conducted by the Collaborative Study Group found that over a 3.5 year follow-up period, patient and renal mortality were lower in patients with insulin dependent diabetes mellitus who were treated with captopril, an angiotensin-converting enzyme inhibitor, compared with those who received a placebo.

The average cost of peritoneal or hemodialysis is $50 000 to $58 000 per patient year. The cost of dipstick analysis is $0.30 per test. It was estimated that the cost of screening the adult population in Canada would be equivalent to the cost of caring for 150 hemodialysis patients for 1 year.

Recommendations
Recommendation grade [A, B, C, D, E]  and level of evidence [I, II-1, II-2, II-3, III] are indicated after each recommendation. Citations in support of individual recommendations are identified in the guideline text.

Validation
This report was externally peer-reviewed. The recommendation not to screen the general population is consistent with that of the 1989 U.S. Preventive Services Task Force.

Sponsors
The Canadian Task Force on Preventive Health Care developed this guideline with funding from Health Canada.

Source Document
Nagai R, Wang EEL and Feldman W. Dipstick proteinuria screening of asymptomatic adults to prevent progressive renal disease. In: Canadian Task Force on the Periodic Health Examination. Canadian Guide to Clinical Preventive Health Care. Ottawa: Health Canada, 1994; 436-45.