Evaluation of biochemical markers of renal dysfunction in prostate disorders and healthy controls

Aims & Objectives: Prostate disorders like prostatitis, Benign prostatic hyperplasia (BPH) and prostatitis are the most common disorders of the male population, the latter two being prevalent in the elderly men.PSA being the gold standard parameter to identify these diseases, is not of much importance in the differential diagnosis of prostate disorders. This study focuses on the blood levels of PSA, Urea, BUN, Creatinine BUN/creatinine ratio and eGFR in various disorders of prostate and healthy controls. 
Methodology: Serum sample obtained from 25 patients each, diagnosed to have prostatitis, BPH and carcinoma prostate were analysed for the parameters mentioned above and compared with 75 age matched controls. 
Results: The mean values for PSA as well as other markers of renal function included in the study were statistically significant between cases and controls. Further, significant values in the mean values of all the parameters were also observed in each of the prostate disorders as compared to controls. 
Conclusion: On the basis of our findings, we conclude that patients with prostate disorders are likely to progress into renal dysfunction. Also, based on the results of BUN /creatinine ratio, BPH and cancer of prostate, the most common types of prostatic disorders in old age, are more prone to develop renal dysfunction.


Introduction
The most commonly diagnosed diseases of the prostate include prostatitis, prostatic cancer and benign prostatic hypertrophy. Prostate gland doubles in size during puberty and grows thereafter at around the age of 25. Prostatitis which is classified as acute a nd chronic is an inflammatory condition caused due to bacterial infection which may even spread to the urinary bladder. Prostatic cancer which is the second leading cause of death in elderly men is a consequence of hypermethylation of GSTP1 gene promoter 1 . Non malignant enlargement of the gland with age is referred to as benign prostatic hypertrophy (BPH). Obstruction of urethra is a common symptom in this condition. After the age of 60, 50% of the male populations are likely to develop symptoms of BPH 2 . Conventionally used laboratory markers for the diagnosis of prostate disorders are acid phosphatase and PSA, a glycoprotein produced in the benign and malignant prostate cells. However the latte r has replaced the former with regard to sensitivity and specificity. It was earlier reported that serum creatinine is associated with a high risk of prostate cancer; more so in advanced cases where the chances of survival were low 3 . Some of the biochemical parameters that were reported to be useful in the diagnosis of prostate cancer include free PSA to total PSA ratio 4,5 and serum to urinary PSA ratio 6 . It is evident in the current scenario, that there is a dearth of biochemical parameters for differential diagnosis of prostate disorders, paving way for the identifi cation of newer ones. Since prostate disorders have an association with end stage renal disorders(ESRD) and is also age related 7 , this study focuses on the utility of blood levels of urea, creatinine, BUN , BUN/Creatinine ratio (BCR) and eGFR as a possible aid in the diagnosis of prostate disorders and association of these disorders with renal dysfunction.

Study design
Case control study.

Sample size:
75Patients with high PSA levels (above 4ng/ml),aged between 40-79 years, whose diseases were confirmed by biopsy report. The cases were further grouped as follows Prostatitis (n=25), Benign prostatic hyperplasia(n=25) and Prostatic carcinoma(n=25).50 age matched controls were also enrolled for the study.

Exclusion Criteria
Patients with acute urinary tract infection, smokers, alcoholics, diabetics and kidney disorders. The study was approved by institutional ethics committee and informed consent was taken from all the subjects.

Methodology
5 ml venous blood was collected in a vacutainer and serum used for analysis. PSA was estimated by the method of ECLIA using COBAS e411 8 . Blood Urea was estimated by Urease/ GLDH Method 9 Serum Creatinine was estimated by Jaffe's Method 10 . Estimation of eGFR was based on the following formula 11 Equation

Results
The mean values for PSA as well as other markers of renal function included in the study were statistically significant between cases and controls. (Table 1). Further, significant values in the mean values of all the parameters were also observed in each of the prostate disorders as compared to controls (Table 2).   12 Benign prostatic hyperplasia which is a non malignant condition, is mostly prevalent in older men and is reported to be a maj or cause of lower urinary tract symptoms (LUTS) 13 . The doubling time of this non malignant tumor increases with age 14 . A tumor density of more than 0.15as determined by serial testing of PSA for 2 years, distinguished BPH from prostatic carcinoma 12 .
Acute urinary retention is high in moderate prostate enlargement which can be predicted from the baseline serum PSA levels. It has also been reported that there is a strong correlation between prostate volume and PSA levels and therefore acute urinary rete ntion 15 .However blood urea and creatinine, the markers of acute urinary retention, reported in cases with prostatic carcinoma in our study, which had significantly higher PSA values as compared to other disorders of prostate, did not correlate. This finding is in conformity with the opinion of Weistein et al who have stated an association with chronic kidney disease and urinary bladder outlet obstruction which did not complement wi th prostatic enlargement 16 .
Further, our study indicates that blood levels of urea, creatinine, BUN were highest in prostatitis suggesting maximal renal involvement in this condition, yet eGFR was not proportionately decreased. These findings are conflicting considering the reports of Sampath Kumar et al 17 .
Significant differences in the mean values of blood urea, BUN and BUN/creatinine ratio was more marked in prostate disorders in general, compared to controls. BUN/creatinine ratio was highly significant in cancer of prostate and BPH in particular, amongst the various disorders of prostate, when compared to controls. In support to this observation, it has been stated earlier that many patients with kidney disease responded to surgical treatment of BPH 18 . It has also been reported in earlier studies, that BPH can progress into prostatic cancer 19 .
A BUN/creatinine ratio of >20 was reported to be useful in differentiating pre renal azotemia(PRA) from acute tubular necrosis 20 , but was disagreed later on by Shigehicko et al 21 .
On the basis of our findings, we conclude that patients with prostate disorders are likely to progress into renal dysfunction. Also, based on the results of BUN /creatinine ratio, BPH and cancer of prostate, the most common types of prostatic disorders in old age, are more prone to develop renal dysfunction.