Renal functional reserve in live related kidney donors

Monish Aron; SN Mehta; SC Tiwari; MG Karmarkar; Sandeep Guleria; Rekha Sharma

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ORIGINAL ARTICLE

Year : 2002 \| Volume : 19 \| Issue : 1 \| Page : 63-67

Renal functional reserve in live related kidney donors

Monish Aron, SN Mehta, SC Tiwari, MG Karmarkar, Sandeep Guleria, Rekha Sharma
Departments of Urology, Surgical Disciplines, Nephrology & Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Sandeep Guleria
Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi - 110 029
India

Source of Support: None, Conflict of Interest: None

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Abstract

Objectives: To determine the renal functional reserve in live related donors and compare it with that of normal controls.
Patients and Methods: The study group consisted of 12 subjects who underwent donor nephrectomy at our centre, more than 6 months prior to this study. The control group consisted of 12 healthy, age and sex-matched volunteers who had no previous history of renal disease. The test for renal, functional reserve consisted of a 2 hour baseline creatinine clearance followed by ingestion of 1.2 grains of protein per kg body weight, in the form of cooked red meat, over one hour: A subsequent 2-hour creatinine clearance starting one hour after the completion of protein load was done. Urine collections were meticulously supervised and serum creatinine levels were obtained at the midpoint of each urine collection.
Results: The rise in serum creatinine and creatinine clearance after protein loading was statistically significant in both donors and controls. The test used for estimation for renal, functional reserve was the percent change in creatinine clearance after an acute protein load. This was 26.9 % in the donor population and 29.6 % in the controls. The difference between the 2 groups, therefore, was not statistically significant.
Conclusions: The preservation of renal functional reserve implies that kidney donors are at no significant disadvantage compared to normal healthy people, by virtue of their kidney donation.

Keywords: Renal Functional Reserve; Transplantation; Donor; Kidney

How to cite this article:
Aron M, Mehta S N, Tiwari S C, Karmarkar M G, Guleria S, Sharma R. Renal functional reserve in live related kidney donors. Indian J Urol 2002;19:63-7

How to cite this URL:
Aron M, Mehta S N, Tiwari S C, Karmarkar M G, Guleria S, Sharma R. Renal functional reserve in live related kidney donors. Indian J Urol [serial online] 2002 [cited 2020 Dec 5];19:63-7. Available from: https://www.indianjurol.com/text.asp?2002/19/1/63/21083

Introduction

Kidney transplantation is the treatment of choice for most cases of end stage renal disease. The kidney for transplantation may be obtained from a cadaver donor or a live donor. However, it has been shown that the removal of a critical proportion of the kidney tissue on an experimental animal results in the development of proteinuria, hypertension and progressive uremia.^[1] Compensatory hyperfiltration after the ablation of nephron mass has been shown to adversely affect the function of remaining nephrons in rats.^[2] A high protein diet has been shown to aggravate this by increasing glomerular filtration rate (GFR).^[3]

In view of this, concern has been expressed about the possible long-term effects of reducing nephron mass by 50 % at the time of donor nephrectomy for live related kidney transplantation in man. It is reassuring, therefore, that several groups have now reported a remarkable preservation of renal function in patients who had donated a kidney 10 to 20 years previously.^[4],[5],[6]

However, the mere preservation of renal function is not enough. In healthy subjects there is a capacity in the kidney to increase GFR in response to a variety of conditions such as contralateral nephrectomy, pregnancy and protein ingestion. This capacity is called the renal functional reserve. Ideally, living donors should be used only when we can demonstrate that these people after donor nephrectomy would have a renal functional reserve comparable to that of normal controls and hence are not at a significant disadvantage by virtue of their donor nephrectomy.

After live related donor nephrectomy, the remaining kidney undergoes compensatory hypertrophy and increase in GFR.^[7] The purpose of this study was to determine whether live related donors have a renal functional reserve comparable to that of normal controls.

Materials and Methods

The study consisted of 2 groups : a donor group and a control group. The only selection criteria for these subjects were that they agreed to participate in the study and were non-vegetarians. The donor group consisted of 12 subjects who underwent donor nephrectomy at our center, more than 6 months prior to this study. The donor group comprised 4 males and 8 females. Duration of follow-up ranged from 6 months to 6 years after donor nephrectomy, with a mean of 17.1 months. The mean age of donors at the time of nephrectomy was 50.1 years with a range of 35 to 60 years. The control group consisted of 12 healthy volunteers, mostly hospital staff, who had no previous history of renal disease. Age (to within 10 years) and sex matched controls were used. The body mass index, blood pressures and dietary protein intake were similar in both the donors and the controls.

A full history including dietary history was recorded and physical examination performed. Blood was drawn for baseline serum creatinine and blood urea estimation and urine examination was done. All laboratory estimations were done using standard auto-analyzer techniques. All subjects were fasting on the day of the test. They received a water load (20 ml per kg body weight) prior to the test and urinary losses during the test were replaced with clear fluids every half-hour.

The test [Table - 1] for renal functional reserve consisted of a 2-hour baseline creatinine clearance followed by ingestion of 1.2 gms of protein per kg body weight, in the form of cooked red meat, over one hour. A subsequent 2 hour creatinine clearance starting 1 hour after the completion of protein load was done. Urine collections were meticulously supervised and serum creatinine levels were obtained at the midpoint of each urine collection.

The methodology employed for estimation of creatinine levels used the Jaffe's reaction or alkaline picrate method. The results were analyzed statistically, using the student's t-test and the changes in creatinine clearance before and after the protein load were compared in both donors and controls.

Observations and Results

None of the donors had any untoward symptoms. The physical examination was within normal limits. The postnephrectomy, baseline serum creatinine levels were within the normal range with a mean of 0.89 mg/dl. The mean baseline creatinine clearance was 64.0 ml/min. Corresponding values in controls were a serum creatinine of 0.81 mg/dl and creatinine clearance of 100.25 ml/min. The difference in creatinine clearance in the 2 groups was significant (P<0.05) but the difference in serum creatinine levels was not. Serum creatinine levels in donors showed a significant rise from a pre-nephrectomy mean of 0.67 mg/dl to a post-nephrectomy mean of 0.89 mg/dl. Creatinine clearance in donors showed a significant fall with a post-nephrectomy mean of 64 ml/min against a preoperative mean of 96 ml/min.This represented a 33 % drop in creatinine clearance i.e. the baseline creatinine clearance at follow-up were 67 % of the preoperative values. The rise in serum creatinine and creatinine clearance after protein loading was statistically significant in both donors and controls. The test used for estimation of renal functional reserve was the percent change in creatinine clearance after an acute protein load. This was 26.9 % in the donor population and 29.6 % in the controls. The difference between the 2 groups, therefore, was not statistically significant [Table - 2].

None of the donors showed an increase in urinary protein excretion when compared with the pre-nephrectomy values. Mean blood pressures in donors after nephrectomy were 124 ± 4/82 ± 3 mmHg. When compared with the pre-nephrectomy levels of 124 ± 7/80 ± 6 mmHg, the difference was not found to have statistical significance.

Discussion

A live related transplant has certain distinct advantages over a cadaver one.^[8] These are: a) better short-term and long-term graft survival; b) lower incidence of primary non-function; c) the more elective setting of the operation and shorter waiting period; d) fewer episodes of rejection and infection and; e) shorter hospital stay. The main concerns with live-related transplantation are those of availability and possible deleterious effects on the donor. Experimental studies in animals and studies in humans have provided evidence that as renal mass progressively decreases glomerular hyperfiltration and glomerulosclerosis increases.^[1],[2],[9] This observation may be relevant to the kidney donor because of the sustained increase in renal hood flow and glomerular filtration rate per nephron in the remaining kidney after unilateral nephrectomy. Concern for the donor has also been expressed in reports showing that patients with unilateral renal agenesis can develop focal glomerulosclerosis and progressive failure of their solitary kidney.^[10] It is reassuring, therefore, that several groups have now reported a remarkable preservation of renal function in patients who had donated a kidney 10 to 20 years previously.^{[4],[5],[6],[11]}

In healthy subjects, the glomerular filtration rate is variable under different conditions. This capacity of the kidney to increase its GFR in response to a variety of conditions (uninephrectomy, pregnancy, protein ingestion and amino acid infusion) demonstrates a renal functional reserve. Bosch et al^[12] have suggested that resting glomerular filtration rate is an insensitive index of renal disease. This was highlighted by patients with proven renal disease whose resting glomerular filtration rates were found to be within normal limits.^[13]

Most studies have demonstrated that protein ingestion leads to an increase in GFR and creatinine clearance.^{[7],[12],[14],[15]} Camara et al^[14] and Jones et al^[15] however demonstrated that non-meat proteins do not increase GFR. Jones et al surmised that this might be due to certain differences in amino acid composition. That an amino acid infusion increases GFR has been demonstrated by Graf et al.^[16] However these are expensive and entail the use of an indwelling IV cannula with its attendant risks and complications. Thus to avoid the doubts about the efficacy of vegetarian proteins and the problems with amino acid infusions, we decided to use cooked red meat as the protein source, even though it entailed the use of nonvegetarians only for our study.

Inulin clearance is the gold standard for estimation GFR.^[17],[18] Several groups have found a good correspondence between the inulin and endogenous creatinine clearance in normal subjects.^[14],[19] Hence creatinine clearance is a reliable and simple method for estimation of GFR and was used by us for our study purposes. We used a 2-hour creatinine clearance because urine collection can be meticulously supervised over a brief period and hence the errors inherent in a 24-hour collection avoided. Further, a 2-hour estimation is more convenient than a 24-hour estimation that would require overnight hospitalization for supervised collection. An initial water load was given to ensure adequate urine output during the test period. A urethral catheter was not used for urine collection owing to the risks of infection, trauma and stricture formation.

Several investigators have studied residual function after donor nephrectomy at varying intervals post operatively.^{[4],[5],[6],[11],[20],[21],[22],[23]} Tapson et al,^[7] studied the glomerular filtration rates of 28 donors who underwent nephrectomy up to 22 years previously; before and after a protein load.

A mean renal functional reserve of 24.9% was demonstrated in all cases. There was no evidence of loss of this reserve with time. Cassidy et al^[24] in a study of 12 living related donors found no clinically significant impairment of renal function. Renal functional reserve was observed to be comparable with that of normal controls. Rodriguez-Iturbe et al^[25] however reported that the renal functional reserve in nephrectomized donors, was diminished as compared to normal controls.

Therefore the majority consensus of most investigators is that:

Live related kidney donation is a safe procedure.^[23]
With extended follow-up there may be a slightly in creased incidence of non-progressive, mild, non-albumin proteinuria and hypertension^{[4],[5],[6],[21],[23]} that warrants close follow-up and dietary protein restriction.^[23] In a large long-term study, Anderson et al" found that the prevalence of hypertension in kidney donors was similar to that in the general population, with the exception of male donors aged 50 to 69 years who had a higher frequency of hypertension than did matched controls. The occasional patient who develops severe proteinuria usually has acquired renal disease independent of the kidney donation.^[23]
There is a mild increase in serum creatinine levels and fall in creatinine clearance after donor nephrectomy, but patients have no symptoms attributable to renal dysfunction and the levels still remain within normal range.
Renal function does not deteriorate progressively after nephrectomy, with creatinine clearance remaining stable at approximately 70 percent of predonation value.^[23]
Renal functional reserve is maintained after kidney donation^[7] and is comparable with that of normal healthy controls.^[24]

The observations from our study corroborate these findings. The preservation of renal functional reserve implies that kidney donors are at no significant disadvantage compared to normal healthy people, by virtue of their kidney donation. Although there is a decline in renal function after donor nephrectomy as manifested by a rise in serum creatinine and fall in creatinine clearance (33 %), it is not sufficient to produce clinical symptoms. Hyperfiltration occurs in the remaining kidney of donors since the baseline GFR observed post-nephrectomy is more than half of the preoperative values. Moreover, the remaining kidney is still capable of increasing GFR in response to a meat protein load. There is no evidence of occurrence of proteinuria or hypertension in uninephrectomized donors at least over the time period studied.

References

1.	Chanutin A. Ferris EO. Experimental renal insufficiency produced by partial nephrectomy. Arch Intern Med 1932: 49: 767-787.
2.	Hostetter TH. Olson JL. Rennke HG. Venkatachalam MA et al. Hyperfiltration in remnant nephrone : A potentially adverse response to renal ablation. Am J Physiol 1981: 24: F85-F93.
3.	Brenner BM. Meyer TW. Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in ageing. renal ablation and intrinsic renal disease. N Engl J Med 1982: 307: 652.
4.	Vincenti F. Amend WJC Jr. Kaysen G et al. Long-term renal function in kidney donors : sustained compensatory hyperfiltration with no adverse effects. Transplantation 1983: 36: 626-629.
5.	Hakim RM. Goldszer RC, Brenner BM. ypertension and proteinuria :long-tens sequelae of uninephrectomy in humans. Kidney Int 1984: 25: 930-936.
6.	Miller U. Sudhanthiran M, Riggio RR. et al. Impact of renal donation'⁴⁰ Long-teen clinical and biochemical follow-up of living donors in a single center. Am J Med 1985: 79: 201-208.
7.	Tapson JS. Mansy H, Marshall SM, Tisdall SR, Wilkinson R. Renal functional reserve in kidney donors. Quarterly Journal of Medicine 1986: 60(231): 725-732.
8.	Ferguson RM, Henry ML. Renal transplantation. In Surgery : Principles and Practice. Greenfield U. Mulholland MW. Oldham KT. Zelenock GB (eds). JB Lippincott Co Philadelphia 1993: 517.
9.	Brenner BM. Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney lot 1983: 23: 647-55.
10.	Kiprov DD. Colvin RB, McCluskey RT. Focal and segmental glomerulosclerosis and proteinuria associated with unilateral renal agenesis. Lab Invest 1982; 46: 275-281.
11.	Anderson CF. Velosa JA, Frohnert PP et al. The risks of unilateral nephrectomy: Status of kidney donors 10 to 20 years postoperatively. Mayo Clinic Proc 1985: 60: 367-374.
12.	Bosch JP. Saccaggi A, Lauer A et al. Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate. Am J Med 1983: 75: 843-850.
13.	Balow JE. Therapeutic trails in lupus nephritis. Nephron 1981: 27: 171-176.
14.	Camara AA. Ann KD. Reimer A et al. The twenty-four-hourly endogenous creatinine clearance as a clinical measure of the functional state of the kidneys. J Lab Clin Med 1951; 41: 743-763.
15.	Jones G. Lee K. Swaminathan R. Glomerular filtration response to acute protein load (Letter). Lancet 1985: 2: 838.
16.	Graf H. Stummvoli HF. Luger A. Prager R. Effect of amino acid infusion on glomerular filtration rate (correspondence). N Engl J Med 1983: 308: 159-160.
17.	Gonwa TA. Atkins C. Zhang YA et al. Glomerular filtration rates in persons evaluated as living related donors: Are our standards too high ? Transplantation 1993; 55: 983-985.
18.	Lewis R. Kerr N. Van Buren C et al. Comparative evaluation of urographic contrast media, inulin and 99nn Tc-DTPA clearance methods for determination of glomerular filtration rate in clinical transplantation. Transplantation 1989: 48: 790-796.
19.	Steinitz K. Turkand H. The determination of glomerular filtration by the endogenous creatinine clearance. J Clin Invest 1940: 19: 285.
20.	Slack TK. Wilson DM. Normal renal function: CIN and CPAH in healthy donors before and after nephrectomy. Mayo Clinic Proc 1976: 51: 296-300.
21.	Talseth T. Fauchald P, Skreds S et al. Long-term blood pressure and renal function in kidney donors. Kidney Int 1986: 29: 1072-1076.
22.	Najarian JS. Chavers BM, McHugh LE. Matas AJ. 20 years or more of follow-up of living kidney donors. Lancet 1992; 340: 807-809.
23.	Bay WH and Hebert LA. The living donor in kidney transplantation. Ann Intern Med 1987; 106: 719-727.
24.	Cassidy MID. Beck RM. Renal functional reserve in live related kidney donors. Am J Kid Dis 1988: 6: 468-472.
25.	Rodriguez-Iturhe B, Herrera J, Garcia R. Response to acute protein load in kidney donors and in apparently normal post acute glomerulonephritis patients : Evidence for glomerular hyperfiltration. Lancet 1985: 2: 461-464.