Chronic kidney disease prediction is an inexact science: The concept of “progressors” and “nonprogressors”

Abstract

In 2002, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) instituted new guidelines that established a novel chronic kidney disease (CKD) staging paradigm. This set of guidelines, since updated, is now very widely accepted around the world. Nevertheless, the authoritative United States Preventative Task Force had in August 2012 acknowledged that we know surprisingly little about whether screening adults with no signs or symptoms of CKD improve health outcomes and that we deserve better information on CKD. More recently, the American Society of Nephrology and the American College of Physicians, two very well respected United States professional physician organizations were strongly at odds coming out with exactly opposite recommendations regarding the need or otherwise for "CKD screening" among the asymptomatic population. In this review, we revisit the various angles and perspectives of these conflicting arguments, raise unanswered questions regarding the validity and veracity of the NKF KDOQI CKD staging model, and raise even more questions about the soundness of its evidence-base. We show clinical evidence, from a Mayo Clinic Health System Renal Unit in Northwestern Wisconsin, United States, of the pitfalls of the current CKD staging model, show the inexactitude and unpredictable vagaries of current CKD prediction models and call for a more cautious and guarded application of CKD staging paradigms in clinical practice. The impacts of acute kidney injury on CKD initiation and CKD propagation and progression, the effects of such phenomenon as the syndrome of late onset renal failure from angiotensin blockade and the syndrome of rapid onset end stage renal disease on CKD initiation, CKD propagation and CKD progression to end stage renal disease all demand further study and analysis. Yet more research on CKD staging, CKD prognostication and CKD predictions is warranted. Finally and most importantly, cognizant of the very serious limitations and drawbacks of the NKF K/DOQI CKD staging model, the need to individualize CKD care, both in terms of patient care and prognostication, cannot be overemphasized.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

“…Prediction models in human patients are similarly problematic and subject to bias. 9 Sustained and overt damage to the glomerulus or tubulointerstitium from primary diseases like hypertension, glomerulonephritis, or chronic pyelonephritis which are not fully resolved promote an expected progressive damage and an expected loss of functional kidney mass. The risks, patterns, and mechanisms for progression from seemingly occult CKD remain unknown.…”

“…Similarly, the underlying mechanisms participating in progression have been hypothesized widely but remain largely undefined. 9,10 Regardless of which pattern or mechanism of CKD progression prevails in an individual patient, all appear to share a common feature of active stress or injury to the residual structures of the kidney.…”

Diabetic Nephropathy and CKD—Analysis of Individual Patient Serum Creatinine Trajectories: A Forgotten Diagnostic Methodology for Diabetic CKD Prognostication and Prediction

“…Clearly, the assumption is that serum creatinine and eGFR trajectories in CKD patients generally follow a linear, predictable, smoothly progressive, and time-dependent curve to advance through the increasing CKD stages I through V before inexorably reaching ESRD and the need for RRT [ 18 , 19 , 20 , 21 ]. On the other hand, it must be acknowledged that such mathematical predictability of renal functional CKD marching through these incremental projected CKD stages and finally, inexorably ending up in symptomatic ESRD and the need for RRT is unproven, untested, and potentially flawed [ 13 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. We recently completed an exhaustive reexamination of these phenomena regarding CKD behavior and proposed the nomenclature of CKD “progressors” and CKD “nonprogressors” to characterize the true behavior of CKD patients seen in clinical nephrology practice [ 21 ].…”

“…The following case report demonstrates the ability of CKD patients with diabetic nephropathy to remain at a later stage CKD, over long periods of time, sometimes for several years, without any further progression of CKD stages, even in older >65-year-old patients [ 21 ]. Such stability of CKD was demonstrated in a Canadian study previously [ 26 ].…”

“…Such stability of CKD was demonstrated in a Canadian study previously [ 26 ]. These patients represent the so-called CKD “nonprogressors” [ 21 ].…”