Protecting Residual Renal Function

Why is residual renal function important?

The importance of residual renal function (RRF) and its care has gained increased attention recently. A patient who has 2 mL/min of residual urea clearance, a starting point proposed by the Kidney Disease Outcomes Quality Initiative (KDOQI) above which the Kt/V may be adjusted downwards (and time of dialysis reduced), has an addition of about 0.3 Kt/V, which is about 15 percent of the usual weekly dialysis dose, but also adds the benefit of kidney function beyond toxin removal.

Regardless of dialysis modality, the presence of RRF has been associated with increased survival in patients receiving dialysis treatment.(1, 2) The reasons for this survival benefit are not yet completely known but several aspects of two major functions of the kidney are likely to be responsible. Firstly, the excretory function, which gets rid of uremic toxins (both small molecules such as urea but also the small water-soluble fraction of protein–bound toxins) from the plasma, but also removal of extra fluid from the plasma. Secondly, the endocrine functions such as the production of erythropoietin (stimulating and promoting the maturation of blood cells) and vitamin D changes (central to bone and mineral metabolism) are also associated with the presence as of RRF.

Consequently, the decline of RRF affects volume management because more salt and water is kept in the body with consequent increase in blood pressure(3) and left ventricular mass(4) (which is by itself associated with survival.(5) It has also been reported to affect anemia management(4, 6, 7), bone and mineral metabolism(6, 7) and increased inflammation(8). In addition a possible association between decreased vitamin D levels and inflammation has also been proposed recently.(9)

What does lead to loss of residual renal function in dialysis patients?

Several studies have tried to identify predictors of decline of RRF. Hemodialysis seems to be worse than peritoneal dialysis (PD), probably because sudden drops in blood pressure are more likely with hemodialysis because fluid is removed much more quickly during short hemodialysis sessions as compared to the longer treatment cycles in PD. In patients with a form of heart disease called diastolic dysfunction where the heart is stiffer than usual even small decreases in blood pressure could be harmful. A study conducted in the Netherlands showed an association between intradialytic hypotension/decrease in systolic blood pressure and decline of RRF.(10) These findings are corroborated by reported relations between diastolic blood pressure and decline of RRF.(10, 11) A correlation between degree of volume expansion and urine output in a recent report was used as the basis of a suggestion that a certain degree of fluid overload may preserve RRF.(12, 13) This however, should be, in regard of the potentially harmful consequences of fluid overload, be considered extremely cautious. It may also be noted that a recent secondary analysis of the Frequent Hemodialysis Network Trials showed a more rapid decline of RRF in subjects enrolled in the more frequent arm of the trial, which suggests that more frequent hemodialysis may associate to stronger decreases in RRF for reasons which remain to be explained.

In addition to volume related factors, several other factors(10, 14) including gender (particularly female gender as being associated with a stronger decline), non-white race (associated with a stronger decline), dialysis choice, associated illnesses (such as diabetes, hypertension, polycystic kidney disease a congestive heart failure), biomarkers (such as for example high serum phosphate, low serum albumin), and the presence of protein in the urine are associated with a decline in kidney function, Prescriptions of calcium channel blockers, ACE inhibitors, HMG-CoA reductase inhibitors appear be related to preservation of RRF (14). A randomized trial in Japan showed a favorable effect of valsartan (angiotensin receptor blocker) on RRF.(15)

What can be done to preserve RRF in dialysis patients?

There is not enough completed research to answer this question however, scientists at the Renal Research Institute continue to investigate this problem. As in many other aspects of health and disease lifestyle modification such as stop smoking (smoking substantially affect the perfusion of the kidney), weight loss and sodium restriction appear to be of benefit. A relationship between a positive (dialytic and dietary) sodium mass balance and fluid intake (and subsequent ultrafiltration rates) has been reported, which again may translate into a steeper decline of RRF. Thus particularly the latter will be helpful to reduce interdialytic weight gains and the elimination of a potentially harmful factor. Along these lines optimal volume management may be assumed to affect other potential factors increasing RRF decline. This would include the use of objective measures of diagnosis of fluid overload, such as bioimpedance techniques and possibly more effective ultrafiltration (emphasizing treatment prolongation in the presence of high ultrafiltration rates). Remember that salt restriction will lead to less thirst and less fluid gain. Use of medications such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, N-acetylcysteine are suggested to potentially be of benefit but more research in prospective randomized settings is needed to determine definite recommendations.

In summary: RRF increases the probability of survival and every effort should be made to preserve it for as long as possible.

References

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3. Menon MK, Naimark DM, Bargman JM, Vas SI, Oreopoulos DG. Long-term blood pressure control in a cohort of peritoneal dialysis patients and its association with residual renal function. Nephrol Dial Transplant. 2001 Nov;16(11):2207-13.
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11. Brazy PC, Stead WW, Fitzwilliam JF. Progression of renal insufficiency: role of blood pressure. Kidney Int. 1989 Feb;35(2):670-4.
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13. Davenport A, Sayed RH, Fan S. Is extracellular volume expansion of peritoneal dialysis patients associated with greater urine output? Blood Purif. 2011;32(3):226-31.
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15. Suzuki H, Kanno Y, Sugahara S, Okada H, Nakamoto H. Effects of an angiotensin II receptor blocker, valsartan, on residual renal function in patients on CAPD. Am J Kidney Dis. 2004 Jun;43(6):1056-64.