| 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 2020 Jul 2];16:556-61. Available from: http://www.sjkdt.org/text.asp?2005/16/4/556/32847
| Introduction|| |
Renal transplantation is an established method of renal replacement therapy in patients with end-stage renal failure. , 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. 
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|| |
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|| |
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|| |
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|| |
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. ,, [6,,,,,,,, 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. ,,,,,,, Furthermore, recent experimental data suggest that protei nuria itself may cause renal injury. , 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.  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). ,,
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.  Treatment that may diminish the adverse consequences of proteinuria is available. ,,,,,, 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.
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Muhammad Ziad Souqiyyeh
Saudi Center for Organ Transplantation, P.o.Box.27049, Riyadh11417
[Table - 1], [Table - 2]