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Saudi Journal of Kidney Diseases and Transplantation
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ARTICLES Table of Contents   
Year : 2005  |  Volume : 16  |  Issue : 4  |  Page : 556-561
Post-Renal Transplant Proteinuria: The Saudi Experience


1 Saudi Center for Organ Transplantation, Riyadh, Saudi Arabia
2 Jeddah Kidney Center, Jeddah, Saudi Arabia
3 Riyadh Armed Forces Hospital, Riyadh, Saudi Arabia

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   Abstract 

We conducted this study to evaluate the risk factors for proteinuria in renal transplant patients. We reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia, transplanted between January 1979 and November 1998. The recipients were grouped according to the presence and magnitude of proteinuria: group I; from zero-0.3 g/L, group II; from 0.4-1.0 g/L, group III; more than one g/L. The records of 340 patients were reviewed in this study. The mean age of the study patients was 39.7 years and the mean duration following transplantation was 82.2 months. There were 209 (61.5%) patients in group I, 92 (27.1%) patients in group II and 39 (11.5%) patients in group III. There was no significant difference among the three groups in terms of mean age, mean duration after transplantation, type of donor (living-related and unrelated, or cadaver), rate of re-transplantation (8.2%), prevalence of hypertension while on dialysis (66.6%), etiology of original renal disease, incidence of acute rejection in the first year, occurrence of diabetes after transplantation (30.6%), or mean serum level of cholesterol (5.9 mmol/L). In comparison to the other groups, group I had significantly more females (44.5 %), more patients with blood pressure within normal limits with or without treatment (56% versus 38% and 17% respectively), lower mean serum creatinine (125 µmol/L versus 149 and 173 µmol/L respectively), higher mean cyclosporine dose (3.28 versus 2.7 and 2.73 mg/kg/day respectively), higher mean prednisolone dose (0.15 mg/kg/day) and less frequency of abnormal electrocardiogram (10% versus 22% and 25% respectively). We conclude that the prevalence of post-transplant proteinuria is high in our study patients. Also, our study suggests that proteinuria may be a marker of renal dysfunction and cardiovascular disease in this group of patients. Further studies are required including allograft histology to delineate better the causes and consequences of post-transplant proteinuria.

Keywords: Renal Transplantation, Proteinuria, Cyclosporine

How to cite this article:
Souqiyyeh MZ, Shaheen FA, Sheikh I, Al-Khader AA, Fedhail H, Al-Sulaiman M, Mousa D, Al-Hawas F. Post-Renal Transplant Proteinuria: The Saudi Experience. Saudi J Kidney Dis Transpl 2005;16:556-61

How to cite this URL:
Souqiyyeh MZ, Shaheen FA, Sheikh I, Al-Khader AA, Fedhail H, Al-Sulaiman M, Mousa D, Al-Hawas F. Post-Renal Transplant Proteinuria: The Saudi Experience. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2019 Jul 21];16:556-61. Available from: http://www.sjkdt.org/text.asp?2005/16/4/556/32847

   Introduction Top


Renal transplantation is an established method of renal replacement therapy in patients with end-stage renal failure. [1],[2] Despite the improvement achieved in the overall patient and graft survival rates following renal trans­plantation, some medical problems related to the grafts such as proteinuria are encountered.

Transient proteinuria is common and is often observed in association with episodes of acute allograft rejection. Transient proteinuria may not affect allograft or patient survival independent of its underlying cause. Persistent proteinuria is usually defined as protein excretion of > 0.5 to 1.0 g/24 hours for at least three to six months. [3]

The etiology of post-transplant protienuria is multifactorial. Dysfunction of the renal allograft and immunosuppressive therapy are usually added to the common risk factors such as diabetes.

There have been few reports about the prevalence of protienuria in the general popu­lation in Saudi Arabia. However, to the best of our knowledge, there have been no reports about the prevalence of proteinuria among renal transplant recipients in this country.

In this study, we attempt to evaluate the prevalence and risk factors of protienuria in the renal transplant population being followed­up in two major centers in Saudi Arabia.


   Patients and Methods Top


We reviewed the records of the active renal transplant patients at two large transplant centers in Riyadh and Jeddah in Saudi Arabia transplanted between January 1979 and November 1998.

The review of history included type of donor, original kidney disease, hypertension on dialysis and after transplantation, diagnosis of renal artery disease in the graft, number of acute rejections in the first year and occurrence of cerebrovascular accidents. The review of the physical examination included the measure­ment of blood pressure and body weight.

The laboratory data reviewed included plasma cholesterol levels, electrocardiogram, last three consecutive measurements of serum creatinine level, and 24-hour urine protein excretion. The review of current therapy included the type and dosing of immunosuppressive and anti-hypertensive drugs.

The recipients of renal transplants were grouped according to the presence of protei­nuria: group I; from zero-0.3 g/L, group II; from 0.4-1.0 g/L, group III: more than 1.0 g/L.


   Statistical Methods Top


We used the analysis of variance (ANOVA) to compare the equality of means for any three or more groups of quantitative variables such as age, weight, plasma creatinine etc. The two sample independent t-test was used to compare the equality of means for any two groups. Chi­square test was used to compare categorical variables such as sex, type of transplant etc. The P value was set as significant if below 0.05.


   Results Top


The records of 340 patients were included in the study. There were 226 (66.5%) males and 114 (33.5%) females with a mean age of 39.7± 12.3 years (range 4-76 years). The mean weight of the patients was 66.9 ± 16.4 Kg. [Table - 1] shows the year of transplantation of the study patients.

The mean duration following transplantation, when the data were reviewed, was 82.2 ± 40.1 months. The renal grafts were from cadaver donors in 88 (26.1%), living related donors in 135 (39.9%), and living non-related in 117 (34.0%) of the recipients. There were 316 (96.3%) study patients who had renal transplantation for the first time, while 24 (3.7%) recipients had more than one renal transplant.

The original renal disease was unknown (bilateral small kidneys by ultrasound) in 183 (54.0%) recipients, while hypertension as a cause of renal failure of the original kidneys was diagnosed in 84 (24.8%) patients and 36 (10.4%) with diabetes. Other congenital and primary kidney diseases were diagnosed in 37 (10.8%) patients. Post-transplant diabetes mellitus was seen in 75 (22.2%) of the study patients. Acute rejection episode occurred once in 97 (28.5%) and twice or more in six patients (1.7%). Five patients were recorded to having had cerebrovascular accident after transplantation and seven other patients had allograft renal artery stenosis.

The mean serum creatinine was 231.8 ± 207 µmol/L and the mean 24-hour urine protein was 0.54 ± 0.96 g/L at the end of follow-up.

Electrocardiogram (ECG) was available in 322 patients; 302 (94.1%) were within normal limits, while ECG findings compatible with left ventricular hypertrophy, ischemia and/or left ventricular strain were evident in 19 (5.9%).

All the study patients except 14 (4.2%) were on cyclosporine the mean dose of which was 3.3 ± 1.7 mg/kg/day. There were 170 (58.8%) patients receiving azathioprine and seven (2.0%) were receiving mycophenolate mofetil. Calcium channel blockers were the most frequently used antihypertensives followed by beta-blockers and angiotensin converting enzyme inhibitors (46%, 32%, 10% respect­ively), singly or in combination.

According to the 24-hour urine protein, there were 209 (61.5%) patients in group I (minimal proteinuria), 92 (27.1%) patients in group II (moderate proteinuria) and 39 (11.5%) patients in group III (severe proteinuria).

There was no significant difference among the study groups in terms of mean age, mean duration after transplantation, type of donor (living-related and unrelated, or cadaver), rate of re-transplantation (8.2%), prevalence of hypertension on dialysis (66.6%), etiology of original renal disease, incidence of acute rejection in the first year, diagnosis of diabetes after transplantation (30.6%), or mean serum level of serum cholesterol (5.9 mmol/L).

[Table - 2] shows that in comparison to the other groups, group I patients with minimal proteinuria had significantly more females (44.5%), more patients with blood pressure within normal limits with or without treatment (56% versus 38% and 17% respectively), lower mean serum creatinine (125 µmol/L versus 149 and 173 respectively), higher mean cyclosporine dose (3.28 versus 2.7 and 2.73 mg/kg/day respectively), higher mean prednisolone dose (0.15 mg/kg/day) and less frequency of ab­normal electrocardiogram (10% versus 22% and 25% respectively).


   Discussion Top


This is probably the first report about the prevalence and risk factors of proteinuria in the renal transplant population being followed­up in Saudi Arabia.

The estimated prevalence of moderate to severe proteinuria in our study patients was 39%. The prevalence of significant proteinuria in our study patients was higher than the 10 to 25% prevalence reported by a number of epidemiologic studies that have examined the incidence of persistent proteinuria among renal transplant recipients. [4],[5], [6,[7],[8],[9],[10],[11],[12],[13],[14] Transient proteinuria, resulting from acute rejection or other causes, may not be associated with decreased graft survival rates, unlike persistent proteinuria. Causes of persistent proteinuria include chronic allograft nephro­pathy, transplant glomerulopathy, glomerulo­nephritis (de novo or recurrent), diabetic nephropathy and cyclosporine nephrotoxicity.

The capacity to excrete urine that is virtually free of filtered protein is a critical function of healthy kidneys. Proteinuria is a manifestation of renal dysfunction and, when heavy, has important consequences for extracellular fluid volume regulation. The degree of proteinuria also has prognostic and diagnostic implications. Heavy proteinuria is often associated with more rapid deterioration of renal function and is more likely to be associated with pathologic glomerular lesions than with interstitial lesions or anatomic or hemodynamic causes of renal dysfunction. [6],[7],[9],[10],[11],[12],[13],[15] Furthermore, recent experimental data suggest that protei­ nuria itself may cause renal injury. [16],[17] There­fore, it is possible that the often-reported clinical association between proteinuria and the rate of decrease of renal function could be, in part, a direct result of injurious effects of proteinuria. [18] We did not perform renal allograft biopsies in our study. However, we found significant correlation between heavy proteinuria and serum creatinine levels. Furthermore, we found that patients with heavy proteinuria were on lower mean daily doses of cyclosporine than those with minimal proteinuria, which may suggest inadequate immunosuppression and possibility of chronic rejection more than cyclosporine toxicity.

Recurrent diabetic nephropathy is likely to become an increasingly common cause of proteinuria as the number of diabetic patients with long-term graft survival increases. In our study, we found a significant correlation between heavy proteinuria and prevalence of diabetes.

A number of studies in the general population have suggested that proteinuria is an important risk factor for cardiovascular disease (CVD). [19],[20],[21]

We found correlation between the presence of electrocardiographic ischemic changes and heavy proteinuria that suggests more significant cardiovascular disease in this group of the study patients.

Despite the tendency of the study group with heavy proteinuria to have higher mean cholesterol level, the difference from the group with minimal proteinuria did not reach statistical significance.

However, the prevalence of proteinuria in the transplant patients is high enough to give screening tests sufficient positive and negative predictive values. The consequences of persistent proteinuria are of sufficient magnitude to make screening a useful prognostic test.

Indications for, and methods of screening such as, urine dipstick, protein/creatinine ratio and 24-hours collection for proteinuria were recently reviewed. [22] Treatment that may diminish the adverse consequences of proteinuria is available. [23],[24],[25],[26],[27],[28],[29] However, it should be kept in mind that diseased native kidneys may often contribute to low levels of proteinuria and may occasionally account for large amounts of urinary protein excretion.

We conclude that the prevalence of post­ transplant protienuria is high in our study patients. Also, our study suggests that proteinuria may be a marker of renal dysfunction and cardiovascular disease in this group of patients. Further studies are required including allograft histology to delineate better the causes and consequences of post-transplant proteinuria.

 
   References Top

1.Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol 1998;9(11):2135-41.  Back to cited text no. 1    
2.Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. Cardiovascular disease after renal trans-plantation. J Am Soc Nephrol 1996;7:158-65.  Back to cited text no. 2  [PUBMED]  
3.Kasiske B L, Vazquez M A, Harmon W E, et al. Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 2000;11 Suppl 15: S1-86.  Back to cited text no. 3    
4.Cheigh JS, Mouradian J, Susin M, et al. Kidney transplant nephrotic syndrome: relationship between allograft histopathology and natural course. Kidney Int 1980;18:358-65.  Back to cited text no. 4  [PUBMED]  
5.First MR, Vaidya PN, Maryniak RK, et al. Proteinuria following transplantation: Correlation with histopathology and outcome. Transplantation 1984;38:607-12.  Back to cited text no. 5  [PUBMED]  
6.Bear RA, Aprile M, Sweet J, Cole EH. Proteinuria in renal transplant recipients: Incidence, cause, prognostic importance. Transplant Proc 1988;20:1235-6.  Back to cited text no. 6  [PUBMED]  
7.Vathsala A, Verani R, Schoenberg L, et al. Proteinuria in cyclosporine-treated renal transplant recipients. Transplantation 1990;49:35-41  Back to cited text no. 7  [PUBMED]  
8.Castelao AM, Grino JM, Seron D, et al. Pathological differential diagnostics of proteinuria and late failure after renal transplantation. Transplant Proc 1992;24: 110-2  Back to cited text no. 8    
9.Kim HC, Park SB, Lee SH, Park KK, Park CH, Cho WH. Proteinuria in renal transplant recipients: Incidence, cause, and prognostic importance. Transplant Proc 1994;26:2134-5.  Back to cited text no. 9  [PUBMED]  
10.Cusumano AM, Iotti R, Turin M, Davalos M, Jost L, Vilches A. Incidence, etiology and prognostic value of persistent significant proteinuria in kidney transplants [Spanish]. Medicina B Aires 1996;56:346­52.  Back to cited text no. 10    
11.Peddi VR, Dean DE, Hariharan S, Cavallo T, Schroeder TJ, First MR. Proteinuria following renal transplantation. Correlation with histopathology and outcome. Transplant Proc 1997;29:101-3.  Back to cited text no. 11    
12.Hohage H, Kleyer U, Bruckner D, August C, Zidek W, Spieker C. Influence of proteinuria on long-term transplant survival in kidney transplant recipients. Nephron 1997;75:160-5.  Back to cited text no. 12    
13.Perez-Fontan M, Rodriguez-Carmona A, Garcia-Falcon T, Valdes F. Early proteinuria in renal transplant recipients treated with cyclosporin. Transplantation1999;67:561-8.  Back to cited text no. 13    
14.Yildiz A, Erkoc R, Sever MS, et al. The prognostic importance of severity and type of post-transplant proteinuria. Clin Transplant 1999;13:241-4.  Back to cited text no. 14    
15.Massy ZA, Guijarro C, Wiederkehr MR, Ma JZ, Kasiske BL. Chronic renal allograft rejection. Immunologic and nonimmunologic risk factors. Kidney Int 1996;49:518-24.  Back to cited text no. 15    
16.Eddy AA. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. J Am Soc Nephrol 1994;5:1273-87.  Back to cited text no. 16  [PUBMED]  
17.Zoja C, Donadelli R, Colleoni S, et al. Protein overload stimulate RANTES production by proximal tubular cells depending on NF­kappa B activation. Kidney Int 1998;53:1608-15.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Perna A, Remuzzi G. Abnormal permeability to proteins and glomerular lesions: a meta­analysis of experimental and human studies. Am J Kidney Dis 1996;27:34-41.  Back to cited text no. 18  [PUBMED]  
19.Kannel WB, Stampfer MJ, Castelli WP, Verter J. The prognostic significance of proteinuria: The Framingham study. Am Heart J 1984;108:1347-52.  Back to cited text no. 19  [PUBMED]  
20.Bulpitt CJ, Beevers DG, Butler A, et al. The survial of treated hypertensive patients and their causes of death: a report from the DHSS hypertensive care computing project (DHCCP). J Hypertens1986;4:93-9.  Back to cited text no. 20  [PUBMED]  
21.Samuelsson O, Wilhelmsen L, Elmfeldt D, et al. Predictors of cardiovascular morbidity in treated hypertension: results from the primary preventive trial in Goteborg, Sweden. J Hypertens 1985;3:167-76.  Back to cited text no. 21  [PUBMED]  
22.Keane WF, Eknoyan G. Proteinuria, albuminuria, risk, assessment, detection, elimination (PARADE): a position paper of the National Kidney Foundation. Am J Kidney Dis 1999;33:1004-10.  Back to cited text no. 22  [PUBMED]  
23.Bochicchio T, Sandoval G, Ron O, Perez­Grovas H, Bordes J, Herrera-Acosta J: Fosinopril prevents hyperfiltration and decreases proteinuria in post-transplant hypertensives. Kidney Int 1990;38:873-9.  Back to cited text no. 23    
24.Rell K, Linde J, Morzycka-Michalik M, Gaciong Z, Lao M. Effect of enalapril on proteinuria after kidney transplantation. Transpl Int 1993;6:213-7.  Back to cited text no. 24  [PUBMED]  
25.Barnas U, Schmidt A, Haas M, Oberbauer R, Mayer G. The effects of prolonged angiotensin-converting enzyme inhibition on excretory kidney function and proteinuria in renal allograft recipients with chronic progressive transplant failure. Nephrol Dial Transplant 1996;11:1822-4.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]
26.Borchhardt K, Haas N, Yilmaz N, et al. Low dose angiotensin converting enzyme inhibition and glomerular permselectivity in renal transplant recipients. Kidney Int 1997;52:1622-5.  Back to cited text no. 26  [PUBMED]  
27.Lufft V, Kliem V, Hamkens A, et al. Antiproteinuric efficacy of fosinopril after renal transplantation is determined by the extent of vascular and tubulointerstitial damage. Clin Transplant 1998;12:409-15.  Back to cited text no. 27  [PUBMED]  
28.Calvino J, Lens XM, Romero R, Sanchez­Guisande D. Long-term anti-proteinuric effect of losartan in renal transplant recipients treated for hypertension. Nephrol Dial Transplant 2000;15:82-6.  Back to cited text no. 28    
29.Moore RR Jr, Hirata-Dulas CA, Kasiske BL. Use of urine specific gravity to improve screening for albuminuria. Kidney Int 1997; 52: 240-3.  Back to cited text no. 29    

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Correspondence Address:
Muhammad Ziad Souqiyyeh
Saudi Center for Organ Transplantation, P.o.Box.27049, Riyadh11417
Saudi Arabia
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PMID: 18202510

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    Patients and Methods
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