Pam Harrison

May 31, 2016

VIENNA — Remission is almost as common as progression over a 5-year period in patients with stage 3 chronic kidney disease who are managed by primary care practitioners in the United Kingdom, new research suggests.

"The criteria we used for remission of chronic kidney disease are actually the reverse of the diagnostic criteria," said Adam Shardlow, research fellow and PhD candidate at the Royal Derby Hospital in the United Kingdom. "Essentially, participants at all three time points of the study had no evidence of chronic kidney disease and wouldn't have been diagnosed with it on the basis of their estimated glomerular filtration rate [eGFR]."

He was quick to point out that this was not a case of "misclassification" because patients had met the diagnostic criteria for chronic kidney disease prior to study enrolment.

"What our findings suggest is that there is a lot of variability in measured creatinine results, and the small changes in blood test results produce big changes in eGFR. We're probably not as good as we think we are at estimating kidney function in this category of patients," he told Medscape Medical News.

The study was presented here at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 53rd Congress.

The Renal Risk in Derby study was a prospective cohort trial of 1741 patients recruited from general practices around the United Kingdom from 2008 to 2010.

All met the KDIGO criteria for stage 3 chronic kidney disease — namely, two eGFR measurements below 60 mL/min per 1.73 m² over a 90-day period, Shardlow reported.

Patients were assessed at baseline, at 1 year, and at 5 years. Kidney function was fairly well preserved at baseline, when mean eGFR was 52.5 mL/min per 1.73 m². Mean age at baseline was 73 years.

At the three assessment points, participants were considered to have gone into remission if they had an eGFR above 60 mL/min per 1.73 m² and a ratio of albuminuria to creatinine below 3 mg/mmol.

Conversely, progression was defined as a 25% reduction in eGFR and a change in eGFR category or an increase in albuminuria.

Blood pressure was well controlled at baseline, at a mean of 134 mm Hg for systolic blood pressure and of 73 mm Hg for diastolic blood pressure.

Five-Year Outcomes

At 5 years, 19.3% of the patients met the criteria for remission and 17.7% of the patients met the criteria for progression.

During the 5-year follow-up period, 34.1% of the patients neither regressed nor progressed, but almost 15% died before their final 5-year visit. Approximately 15% of the patients were also lost to follow-up.

"Only four patients developed end-stage renal failure by year 5 — that's less than 1% of the overall cohort — so the development of ESRD in a cohort such as this one is definitely a rarity," Shardlow said.

Multivariable predictors for remission included higher baseline eGFR, lower age at baseline, lower urinary albumin-to-creatinine ratio, and a greater increase in eGFR in the first year of the study.

"CKD remission may have a range of different explanations," Shardlow explained. It might represent a genuine improvement in kidney function over time or an adaptation to previous renal damage, he suggested. Alternatively, it might simply represent variability in kidney function related to the estimate equations used to measure eGFR and serum creatinine.

"In primary care, stage 3 chronic kidney disease is probably a low-risk category overall, and risk prediction tools should be used to identify those at high risk for progression, as well as those at low risk for progression, so as to better advise patients on the relative importance of their condition," he said.

As we all know, chronic kidney disease is "incredibly variable," he added. There is urgent need for international consensus on the definition of remission.

International Definition Needed

Richard Glassock, MD, from the University of California, Los Angeles School of Medicine, said he agrees that an international definition would help.

"Unfortunately, the trial did not include an analysis of the emergence of sarcopenia, which is an important element in individuals of this age over a 5-year period," he told Medscape Medical News.

If patients are protein-deprived or muscle-wasted — quite common in the elderly — dietary protein depletion and the loss of muscle mass can lead to a "marked disparity" between estimated kidney function and actual measured kidney function, Dr Glassock explained.

For example, he said, he would give protein to a patient with a low eGFR in his own practice to see if dietary protein replenishment would change the eGFR.

Very often, he pointed out, he has seen large increases in eGFR after protein has been consumed, enough to eliminate a diagnosis of chronic kidney disease.

This suggests that patients in this study might have had "pseudo" chronic kidney disease before study enrolment, Dr Glassock pointed out.

"This is why it's important to have a measure of protein metabolism, as well as a measure of muscle metabolism, if you are going to define remission," he said.

"But this is still a very important paper," he said.

The study was funded by the Dunhill Medical Trust, the British Renal Society, and Kidney Research UK.

European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 53rd Congress: Abstract MO032. Presented May 23, 2016.

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