1453.pdf 848 | Sindh Institute of Urol- ogy and Transplantation (SIUT), Civil Hospital, Karachi, Pakistan Manzoor Hussain, Altaf H. Hashmi, Syed Adeebul Hassan Rizvi Problems and Prospects of Neglected Renal Calculi in Pakistan Can This Tragedy be Averted? Corresponding Author: Manzoor Hussain, MBBS; MS Department of Urology, Sindh Institute of Urology and Transplantation, Civil Hospital, Karachi, 74200, Pakistan Tel: +92 219 498 9172 Fax: +92 213 272 6165 E-mail: info@siut.org Received May 2012 Accepted November 2012 Purpose: To report our recent experience of treating patients with stones associated with renal failure, some of the factors underlying this problem, and few suggestions to avert this tragedy. Materials and Methods: From January 2010 to December 2010, a total of 2838 new patients with stone disease and renal failure were reviewed and compared with a cohort of 878 patients with normal renal functions. Their demographic and clinicopathological parameters were noted and analyzed. Results: Of 2838 patients, 278 presented with acute and chronic renal failure, 40 (1.4%) with unilateral non-functioning kidneys, and 25 (0.8%) with pyonephrosis and perinephric abscess. Management in 278 (9.7%) subjects was divided into initial relief of obstruction by percutaneous - gery, percutaneous nephrolithotomy, extracorporeal shockwave lithotripsy, and ureterorenoscopy to make these patients stone-free. Results of treatment showed that 72% of patients either recov- ered their renal functions or became dialysis-free at the end of the follow-up period. Conclusion: Complications of renal calculi in the era of modern treatment can be prevented by public education and organizing courses for family physicians as well as opening new stone clin- ics in the rural areas of the country equipped with modern treatment facilities and strategies for prevention of renal calculi. Keywords: kidney calculi, renal failure, anuria, Pakistan ENDOUROLOGY AND STONE DISEASE Endourology and Stone Disease 849Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L INTRODUCTION Stone disease is one of the common causes of obstruc-tive uropathy and nephropathy in Pakistan, which affects all age groups, including children, adults, and elderly.(1) The impact of the obstruction due to stone is - line condition of the kidneys, the potential for recovery, and the presence of infection.(2) Stone disease is not only the cause of pain and infection, (3) Renal failure (RF) due to stone disease could be caused by long standing obstruction, infection, and irritation due to crystals in the renal tubules, or associated medical conditions like diabetes and hypertension, or previous procedures done on the kidney for removal of stones.(4) Neglected renal calculi is a different entity in Pakistan, be- cause on one hand, there is increasing incidence of stone disease and on the other hand, the inadequate facilities for treatment result in very late presentation with large and multiple calculi with RF or any other complication. In the last 30 years, advances in the management of stone disease in the form of extracorporeal shockwave lithotripsy (ESWL), percutaneous nephrolithotomy (PCNL), ureter- orenoscopy (URS), retrograde intrarenal surgery (RIRS), and laparoscopy have diminished the role of open stone surgery all over the world.(5) Unfortunately, in spite of ad- vances, the number of patients with stone presenting with complications is on rise in the public sector hospitals in Pa- kistan.(6) The reported life-threatening complication rate due to stone disease is about 12%.(7) The management of this group of the patients is a challenge and multi-disciplinary. Although various endourologic methods can be applied to make these patients stone-free,(8) open surgery remains cost-effective. (3) Previous report from our institute showed that the frequen- cy of RF in patients with renal calculi was about 8% and frequency of end-stage renal disease due to stone disease was 7.3 %.(1) Similarly, 5.3% of acute RF was due to ure- teral and renal calculi.(6) Other investigators have also re- ported the problems of both acute and chronic RF due to stone disease from other parts of the country.(9,10) Literature review shows that the problem of RF due to stone disease also exists in other developing countries, such as India(8) and China,(11) but rarely in Western countries.(12) Herein, we report our recent experience of treating patients with stones associated with RF, some of the factors underly- ing this problem, and few suggestions to avert this tragedy. MATERIALS AND METHODS were registered for treatment at this institute from January 2010 to December 2010. This descriptive study was carried out on 278 patients who presented with RF and were admit- ted in the ward for treatment. A group of 878 patients with stone with normal renal functions, who were admitted in the ward for management, was taken as control group to study co-morbidities and site of stones in these groups. Rest of the patients (1682) were managed as outpatients in the stone clinic and lithotripsy departments. At the time of admission, full history taking, physical ex- amination, ultrasonography of the kidneys, and the kidney, ureter, and bladder (KUB) x-ray were performed in every subject. Blood chemistry, complete hemogram, and serum urea, creatinine, and electrolytes were evaluated. Urine analysis and culture/sensitivity were done if patients were not anuric. After investigations, the patients were evaluated jointly by a nephrologist, urologist, and radiologist. If urea and creati- nine were >200 mg/dL and >10 mg/dL, respectively, serum potassium would be >5.5 mEq/L and HCO3 <15 mEq/L or if acidosis was present on arterial blood gas analysis, then hemodialysis would be done as an initial treatment. If re- nal functions were within acceptable level for anesthesia and patients were afebrile, then double-J (DJ) stents with or without URS were used to relieve the obstruction. - oes, PCNL would be done under local anesthesia to relieve the obstruction and to drain the infection. In some patients, bilateral PCNL was done. Once patients were stabilized were done in the form of ESWL, URS, PCNL, and open surgery depending on the indications. Neglected Nephrolithiasis in Pakistan | Hussain et al 850 | were followed up in stone clinic with ultrasonography, renal function tests, urine for culture/sensitivity, and KUB x-ray after discharge from the ward. Pre- and postoperative serum were compared to study the effect of relief of obstruction. If they would be prepared for live-related renal transplanta- tion. During hospitalization in the ward, these patients were managed jointly by nephrologists, urologists, infectious disease team, and anesthetists. who present very late with complications, such as RF, pyo- nephrosis, and perinephric abscess. We hypothesized that - velopment of RF in patients with stone. RESULTS Two hundred and seventy-eight (9.7%) patients presented with pyonephrosis or perinephric abscess and 40 (1.4%) with unilateral non-functioning kidneys, while remaining 2560 (90.2%) had normal renal functions (serum creatinine <1.5 mg/dL). Of 278 patients with RF, 200 (72.3%) were from rural areas, while 78 (27.7%) were from urban areas of the country. Two hundred and fourteen (77.6%) subjects belonged to poor socioeconomic class. There were 193 (69.4%) men and 85 (30.5%) women with male-to-female ratio of 2.2:1. Similarly, 878 patients with renal stones with normal re- nal functions (control group) were evaluated for male-to- female ratio, which was found to be 1.4:1. The duration of symptoms of renal calculi and RF ranged from <1 month to >4 years. Ninety patients presented early with duration of <1 month; these patients had symptoms of acute RF with duration of anuria ranging from 2 to 8 days. The causes of delay in diagnosis and neglect were analyzed in 278 patients. It showed that 12% of patients had silent causes included family physicians (19%), hakims, homeo- paths and quacks (24%), and dentists (45%). The site of stones in 278 patients with RF was bilateral renal or ureteral in 158 (55.6%) patients. Similarly, of 878 control patients, 197 (21.6%) had bilateral disease (Table 1). Analysis of co-morbid conditions in 278 patients with RF showed that 35 (12.5%) were diabetics, 55 (21%) were hy- pertensive, and 4 (1.4%) were both diabetic and hyperten- sive. Seventeen (6.1%) had radiolucent stones. Comparison of co-morbidities in the patient and control groups is shown in Table 2. Management in 278 patients with stone with RF was di- 113 (40.6%) subjects, PCNL was done to relieve obstruc- Endourology and Stone Disease Table 1. Comparison of site of stones in the study and the control groups. Site of stones Study group (n = 278) Control group (n = 878) P Number (%) Number (%) Bilateral renal 108 (38.8) 152 (17.3) .0001 Bilateral ureteral 33 (11.8) 39 (4.4) .0001 Bilateral renal + Bilateral ureteral 8 (2.8) 1 (0.1) .0001 Bilateral renal + Unilateral ureteral 9 (3.2) 5 (0.56) .001 Unilateral ureteral 29 (10.4) 153 (17.4) .005 Unilateral renal 49 (17.6) 437 (49.7) .0001 Uniteral renal + Ureteral 31 (11.1) 45 (5.1) .0001 Unilateral renal + Bladder 5 (1.8) 8 (0.9) .22 Ureteral + Vesical - 6 (0.6) .16 Bilateral renal + Bladder 1 (0.3) 24 (2.7) .18 851Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L tion and in 19 (6.8%), URS and DJ stent were success- ful, but 103 (37%) patients presented with severe uremic symptoms; therefore, hemodialysis was needed, while in 43 (15.4%), conservative medical treatment consisting of hy- dration, antibiotics, and correction of electrolyte imbalance was done. in 278 patients. In 158 (56.8%) subjects, open surgery was performed while PCNL was done in 18 (6.4%) and ESWL ureteral calculi included URS in 33 and URS + DJ stent + ESWL in 15 patients; the rest were treated by open surgery (Table 3). Pre- and postoperative serum creatinine levels were availa- ble in 220 patients; remaining patients either died or under- went renal transplantation. Pre-operative serum creatinine ranged from 1.6 to 28 mg/dL with mean serum creatinine of 10.7 mg/dL, while at 3 months postoperative follow-up, serum creatinine ranged from 0.6 to 8.0 mg/dL with mean value of 2.76 mg/dL. The overall results of surgery in 278 patients showed that 72.3% of patients were dialysis-free at the end of the follow-up, 14% received renal transplanta- tion, and 10.4% died till 2010 (Table 4). Stone analysis in 207 samples analyzed by infrared spec- troscopy showed that 62.5% stones contained calcium oxa- late or calcium phosphate either in pure (16%) or mixed (43.5%) form. Similarly, uric acid stones were seen in 11.1% in pure form and in 17.3% in mixed with other com- pounds constituting 28.3% of samples. Struvite stones were present in 5.6% samples with ammonium hydrogen urate in 3.3% and 2,8-dihydroxyadenine in 0.4% patients (Table 5). DISCUSSION Renal stones presenting very late with complications are quite common in Pakistan and have been very well reported in the past(13) and present literature.(14) There are many rea- sons for this tragedy; one is the silent stones not causing any pain, presenting very late with RF or pyonephrosis. Other is treatment of renal calculi by hakims, homeopaths, and alter- native medicines leading to delay in the diagnosis and treat- ment, and family physicians, who deliberately treat these patients with pain killer drugs and do not try to investigate is the poverty and poor health facilities in rural areas of the country. There are 24 urology centers in public and private sectors with 24 lithotripters, but they are functional only in few centers. The incidence of renal calculi is increasing worldwide and Pakistan is not an execption, but treatment modalities are not increasing in parallel resulting in delay and neglect in the treatment of renal calculi in this country. At Sindh Insti- tute of Urology and Transplantation, a tertiary care center Table 2. Comparison of co-morbids, congenital anomalies, and radiolucency in the study and the control groups. Co-morbids Study group (n = 278) Control group (n = 878) P Number (%) Number (%) DM 35 (12.5) 19 (2.1) .0001 Hypertension 22 (7.9) 16 (1.8) .0001 DM + Hypertension 4 (1.4) 3 (0.3) .04 Adult polycystic kidneys 2 (0.7) - .012 Crossed fused ectopia - 2 (0.2) .42 Horseshoe kidney 1 (0.3) 3 (0.3) .96 Stones with UPJO - 7 (0.7) .44 Radiolucent stones 17 (6.1) 21 (2.3) .002 Pelvic kidney with stones - 2 (0.2) .42 DM, indicates diabetes mellitus; and UPJO, ureteropelvic junction obstruction. Neglected Nephrolithiasis in Pakistan | Hussain et al 852 | for renal and urologic diseases, about 9.8% of all patients with stone present with RF, which is probably the highest number ever reported in the world literature.(8,15) Obvious- shows that in spite of minimally-invasive and non-invasive methods, this complication has not reduced in our recent practice. We can avert this tragedy by opening more com- prehensive stone centers in the country equipped with litho- tripsy machines, facilities for PCNL, ureteroscopy, and fa- cilities for open and laparoscopic surgery, as has happened in developed countries. Comparison of site of stones in RF and control groups showed that RF was more common in patients with bilat- eral stone disease and stones in solitary kidney. It means that patients with bilateral renal calculi need thorough in- vestigations to prevent this tragedy and should be treated on priority basis before they go into complications. In 6 pa- tients, large bladder calculi presented with RF; stones were occupying almost all the capacity of the bladder. Neglected bladder calculus presenting with RF has also been reported from China.(16) Co-morbidities, such as diabetes mellitus, hypertension, and congenital anomalies, were compared between the study and control groups. Patients with RF had slightly higher numbers in co-morbidities, which shows that a mi- nor contributing factor may be a co-morbidity leading to RF. Associated obstruction and stasis caused by congenital anomalies were not a contributing factor in RF. Radiolucent stones were more commonly seen in patients with RF compared to the control group, which shows that uric acid nephropathy may be a contributing factor in this population. This was supported by the stone analysis re- ports in this group of patients. Computed tomography scan played a vital role in diagnosis of these patients. Management of patients with stone and RF is different from the patients with stone and normal renal function. They to drain the infection, but in 19 (6.8%) patients, the uret- eroscopy was directly performed, stones were fragmented, and DJ stents were passed without doing PCNL and he- modialysis. This group of patients was selected carefully due to possibility of septicemia. Careful selection included afebrile patients, normal or near normal electrolytes, and preferably a negative urine culture. Acute renal failure due to ureteral calculi can be treated directly by ureteroscopy, lithoclast fragmentation, and DJ stents, as has been recently reported from China.(11) In 37% of our patients, hemodialy- sis was done as an initial treatment, which showed severe leading to uremia. Initial mode of drainage of obstructed kidneys with RF is controversial; there are advantages and disadvantages of PCNL and DJ stents. Double-J stenting obviates the need for external collection device, but is associated with both- ersome lower tract symptoms and a higher incidence of urinary tract infection, and requires general anesthesia in many cases. However, if the patient has uncorrectable co- agulopathy or platelet abnormality, ureteral stenting is in- Endourology and Stone Disease Table 3. Management of stones with renal failure in 278 patients. Initial Management Number (%) Percutaneous nephrostomy 113 (40.6) DJ stents 19 (6.8) Hemodialysis 103 (37) Conservative 43 (15.4) Definitive Management Extended pyelolithotomy 65 (23.3) Pyelolithotomy + DJ + ESWL 9 (3.2) Pyelolithotomy + URS + DJ 20 (7.1) Anatrophic nephrolithotomy 21 (7.2) Anatrophic nephrolithotomy + URS + DJ 2 (0.7) Pyeloureterolithotomy 4 (1.4) Nephrectomy 31 (11.1) PCNL 26 (9.3) PCNL + URS 2 (0.7 ) ESWL + DJ 13 (4.6) URS + DJ 33 (11.8) URS + DJ + ESWL 15 (5.3) Ureterolithotomy 25 (8.9) Ureterolithotomy + DJ + ESWL 2 (0.7) Cystolithotomy 6 (2.1) Cystolithoclast 2 (0.7) ESWL bladder stone 2 (0.7) DJ indicates double-J; ESWL, extracorporeal shockwave lithotrip- sy; URS, ureterorenoscopy; and PCNL, percutaneous nephroli- thotomy. 853Vol. 10 | No. 2 | Spring 2013 |U R O LO G Y J O U R N A L dicated. Internal stenting requires x-ray exposure; hence, should be avoided in pregnancy. On the other hand, PCNL should be strongly considered in pyonephrosis and in case of DJ stenting failure.(2) model therapy ranging from open surgery to endourology (PCNL, URS, or ESWL). Because of multiple and very large staghorn calculi, these patients are best treated with open surgery due to the following reasons. Open surgery provides higher chances of making these patients stone-free in one sitting, and also drainage of pus with excellent stone- free rates like in our patients. Recently, many studies from India have shown PCNL as the (17,18) We have done PCNL in 18 subjects with renal calculi. In our experience, the rate of redo PCNL was high in cases of multiple renal calculi, which needs multiple general an- esthesia and multiple admissions, and is not cost-effective. Multiple anesthesia and procedures can affect the recovery of renal functions. Furthermore, many patients do not prefer to undergo multiple procedures. The aim of surgery in these patients is to make them stone- and dialysis-free if possible and to get maximum mileage from these chronically ob- structed kidneys to save the cost of dialysis. In our experi- ence, open surgery provides the best chance in experienced hands as compared to PCNL. Overall stone clearance rate after ESWL in these patients was observed to be poor in our study and others.(19) An analysis of the outcome of management at the end of the follow-up showed that 57% of patients either had complete - tive treatment. Another group of 41 (14.7%) remained dial- ysis-free after management with overall 72% of the patients a good achievement in a developing country like Pakistan to save the cost of dialysis in these patients and give them better life with joint management by urologists, nephrolo- gists, and anesthetists at our center. Recovery of renal functions after relief of obstruction pro- vides human model for study of recovery potential as most of the studies reported in the literature are animal-based.(2) Since our center is a public sector renal transplant center in the country, 39 (14%) of the patients received renal trans- plantation in this group, which is an achievement to reha- bilitate these patients back to normal life. Recovery of renal Table 4. Results of treatment (n = 278 patients). Outcomes Number (%) Complete recovery (serum creatinine 0.6 to 1.5 mg/100 mL) 64 (23) Improvement of renal functions (serum creatinine 1.6 to 3 mg/100 mL) 96 (34.5) Renal functions remained stable (dialysis-free) (serum creatinine 3 to 6 mg/100 mL) 41 (14.7) No recovery (Dialysis dependent) 9 (3.2) Renal transplantation 39 (14) Mortality 29 (10.4) Table 5. Stone analysis in the study group (n = 207). Number (%) CaOx (M) + CaP 84 (40.5) CaOx (M) 28 (13.5) CaP 5 (2.4) CaP + Fat + Proteins 2 (0.9) CaOx (D) + CaOx (M) 4 (1.9) CoD + CaP 7 (3.3) UA 23 (11.1) UA + CaOx (M) + CaP 16 (7.7) UA + CoM + AHU 1 (0.4) UA + CaOx (M) 15 (7.2) UA + NaH-Urate 2 (0.9) UA + CoD 2 (0.9) Struvite + CaP 16 (4.7) Struvite 2 (0.9) AHU 2 (0.9) AHU + UA 5 (2.4) 2, 8-Dihydroxyadenine 1 (0.4) CaOx indicates calcium oxalate; M, monohydrate; CaP, calcium phos- phate; D, dihydrate; CoD, calcium oxalate dehydrate; UA, uric acid; CoM, calcium oxalate monohydrate; AHU, ammonium hydrogen urate; and NaH, sodium hydrogen. Neglected Nephrolithiasis in Pakistan | Hussain et al 854 | functions after removal of stones with open surgery has also been reported by other researchers.(20) The mortality in neglected renal stones with RF was seen and irreversible damage due to renal stones. The common causes of mortality in these patients are sepsis and other complications of dialysis and end-stage renal disease.(3) All subjects who recovered their renal functions were regularly followed up in stone clinic with advice on hydration, diet, and treatment of urinary tract infection and hypertension. This strategy helps in stabilizing renal functions and pre- vention of future recurrence.(5) CONCLUSION Our recent data show the increasing number of neglected renal calculi presenting very late for management, which on one hand, is a challenge and on the other hand, a tragedy, which should have been averted in the modern era of shock- wave therapy and endourology. Unfortunately, we have not yet succeeded in averting this tragedy. This tragedy can be avoided by organizing public aware- ness programs in print and electronic media to educate the patients to seek early consultation. Furthermore, educa- tion programs should be organized for family physicians for early diagnosis, treatment, and referral to tertiary care urologic centers. As most of the patients are coming from rural areas and belong to poor socioeconomic class, there is a need to open new stone clinics in these areas equipped ureteroscopy facilities. ACKNOWLEDGEMENTS We acknowledge with gratitude the efforts of Professor Dr. Muhammed Mubarak, Associate professor, Department of Pathology, SIUT, for his critical review of the manuscript and help in the preparation of this paper for publication. CONFLICT OF INTEREST None declared. REFERENCES 1. Rizvi SA, Manzoor K. Causes of chronic renal failure in pa- kistan: a single large center experience. Saudi J Kidney Dis Transpl. 2002;13:376-9. 2. Wilson DR. Pathophysiology of obstructive nephropathy. Kidney Int. 1980;18:281-92. 3. Hussain M, Lal M, Ali B, et al. Management of urinary calculi associated with renal failure. J Pak Med Assoc. 1995;45:205- 8. 4. 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