Nephrolithiasis (NL) is one of the most common disorders affecting a significant proportion of general population and is often incapacitating for an individual.^[1] The mechanism of stone formation and the pathophysiology has differing etiologies. It occurs in almost all regions of the world with no racial or cultural difference. The precise mechanism of stone formation is still debated and the current interventions for the prevention and management of renal stones are not entirely effective. The life time prevalence in men was estimated to be 13% and it is 7% in women and the peak incidence is found to be in the third and fourth decades of life. The increase in the prevalence of renal stones all over the world is attributed to the changing dietary patterns, concomitant increase in the prevalence of diabetes and obesity and even environmental stressors such as a warmer climate owing to accelerated rates of global warming are implicated.

There is a very high recurrence rate of renal stone formation and the rate of recurrence after initial stone formation is reported to be as high as 50% at 5 years and 80 to 90% at 10 years.^[2] People affected with renal stones are more likely to have urinary metabolic abnormalities when compared with healthy individuals, and patients with recurrent stone formation were found to have significant metabolic abnormalities in contrast to patients with a single stone formation.

Nephrolithiasis is often considered as a systemic disorder and is associated with metabolic conditions such as obesity, hypertension, diabetes and metabolic syndrome.^[3] Furthermore metabolic evaluation of renal calculus disease has revealed at least one identifiable and treatable metabolic condition in almost 90% of the test subjects. Based on these recent evidences the current guidelines in renal stone management endorse a change in diet, exercise, weight reduction and to decrease the levels of sodium intake with a shift towards more calcium intake in diet and also to consume adequate amounts of fluids.^[4]

The average rates of likelihood of recurrence of another renal stone after the initial episode were reported to be 30 to 40% in a period of 5 years. Promisingly the recurrence rates of renal calculi have shown a dramatic reduction by more than 50%, as pointed out in several clinical trials. This underscores the role of effective medication and dietary intervention in prevention of recurrent renal stones.^[5]The risk factors for renal stone formation are varied and heterogeneous and an increased risk has been attributed to genetic, dietary and environmental factors. The risk of formation of kidney stone was reportedly 2.5 times higher in individuals with a previous family history.^[5]The predominant characteristic feature of renal stones in almost 80% of the adults is that they are composed of calcium oxalate or calcium phosphate. Struvite and Uric acid stones account for 5 – 10% of the renal stones and cystine stones are reportedly rare.^[6]

In asymptomatic patients nephrolithiasis is often an incidental finding and the presenting symptoms of nephrolithiasis are dysuria, urgency and hematuria.Renal colic with severe abdominal and flank pain is a characteristic clinical sign and is sometimes associated with nausea and vomiting.

Evaluation must include both the individual patient’s risk factors as well as other comorbidities, like diabetes. To address these factors causing recurrence of renal calculi, current recommendations include a change in diet, exercise, weight loss, and a shift toward more dietary calcium, fluids, and less sodium, protein, apart from surgical management aimed at complete stone clearance. The investigations include stone composition studies in addition to biochemical tests which include measurement of calcium, albumin, creatinine, uric acid, potassium, bicarbonate. Urinalysis involves testing for pH, volume, calcium, creatinine, uric acid, oxalate, citrate, sodium.^[7]

This study thereby intends to identify the factors that increase the risk of formation of recurrent renal stones and to describe the clinical presentation in patients. The aims of the present study is to determine the prevalence of determinants of recurrent renal stone formation, to identify the clinical picture and various treatment modalities practiced and to analyze the factors associated with recurrent renal stone formation in relation to medical and dietary management. 

The current study is a prospective interventional study done over a period of eighteen months in the Department of Urology, NRI Medical College and Hospital. Fifty patients admitted in the Department of Urology are taken in the study using the non probability sampling method.The inclusion criteria include those patients with recurrent renal stone disease, needing intervention, patients with previous surgical history for kidney stone disease and patients who underwent ESWL for renal stones, with documented evidence of complete stone clearance.Patients who are first time stone formers, those unfit for surgery and who are on medical management were excluded from the study. Data from the questionnaires was analysed with MS Excel and SPSS Software version 20 for statistical analysis. Bivariate analysis was performed using chi-square test and p – value of less than 0.05 was considered as statistically significant

Most of the study participants belonged to 31 - 40 years of age group (30%), followed by 24% in the 21-30 years of age group and 22% in the 41-50 years of age group. There after there is a decreasing frequency with 18% in the 51-60 years age group and only 4% of the patients had age more than 60 years. (Graph 1)The mean age was found to be 38.19 years with a standard deviation (S.D) of 11.23.Majority of the patients were men (70%) and only 15 (30%) patients are women.

Most of the patients presented with colicky pain as the main symptom (31.9%). Followed by dysuria in 23.1% of the patients, hematuria in 20.9%, fever in 12.1%, vomiting in 9.9% and 2.2% of the patients presented with increased frequency of micturition or incontinence.

Most of the patients (44%) responded that the pain was present for one day to one month followed by patients with a duration of <12 hours (26%). 18% of the patients had a history of pain for more than one month and 12% of the patients complained that the duration of the pain lasted between 12 to 24 hours.

Past history of renal stone disease was present in as many as 66% of the patients between 1 to 5 years of duration, followed by 20% of the patients with less than a year and 14% of the patients with more than 5 years of history. (Graph 2)More than half (64%) of the patients had no existing co – morbid condition. 16% of the respondents were hypertensive and 12% of them had diabetes. Both hypertension and diabetes was present in 6% of the patients. 1 (2%) patient was on treatment for Coronary artery disease (CAD).

All the patients in the study were diagnosed with renal calculi by an USG (100%) followed X-ray KUB (20%) and combined use of USG and X-ray KUB was done on 14% of the patients. Spiral CT scan was used for diagnosis in majority (82%) of the patients after USG and IVP was used for imaging in 18% of the patients in the present study.(Graph 3)

In the present study, most of the patients with renal calculi were managed by PCNL (62%) followed by ESWL (20%). 10% of the patients were managed conservatively and 8% were treated using RIRS.(Graph 4)No open surgery was done in present study.Most of the patients complained of pain (62%), in 18% of the patient’s pain with fever was seen. In 5 (10%) patient’s hematuria was seen as a post-operative complication for which medical management was started for prevention of clot formation. In one patient surgical intervention was needed for clot evacuation under spinal anaesthesia.

On examination of routine urine samples, in 72% of the patients the results were normal, and in 28% of the patients abnormal findings such as presence of casts, blood clots or pus cells are seen.Urine culture was also done for all the samples, and most of the samples had no evidence of bacterial growth (82%). Presence of E.coli was seen in 8% of the samples and proteus was isolated in the remaining 10%.

When the laboratory serum parameters were compared between males and females, there is no significant statistical difference observed (p > 0.05) for all the lab investigations done. (Table 1).

The difference between the two samples of urine collected at the start of the study and the other after 6 months of follow up were noted as shown in Table 2. The results from the analysis reveal that, there is a statistically significant difference (p<0.05) in the volume of urine voided between the two consecutive samples. Similar statistically significant differences were noted between other urinary parameters such as, Citrate, calcium and oxalate (p<0.05). Hypocitraturia was seen in 24% of the patients. However there is no significant difference observed between urinary parameters like, pH, Phosphate, Uric acid, creatinine and sodium (p>0.05).

Biochemical analysis of renal stones was done in 30 patients. The chemical composition of nearly half of the stones were (43%) calcium oxalate (Table 3).30% of the stones are composed of both calcium oxalate and Carbonate and 17% are composed of calcium oxalate and phosphate. The remaining 10% are composed of uric acid.

When medication history was compared with the formation of recurrent stone formation, a statistically significant difference was observed (p<0.05) (Table 4), with higher number of patients (63.3%) using any drugs were found to have recurrent stone formation compared to those who are not using any kind of medication (36.7%). The different kinds of drugs noted were found to be loop diuretics, HIV medication, anti-epileptic medications (Topiramate) and magnesium containing antacids and also proton pump inhibitors.

The patients in the study are grouped according to the duration of the recurrence of renal stones and those with less than or equal to 1 to 5 years are classified into group 1 and those with a duration of more than 5 years are classified as group 2. When various dietary factors are compared with the risk of recurrent stone formation, less water consumption of only 2-3 L, excessive salt intake were found to be statistically significantly associated (p<0.05), Table no.18.It was also observed that, the risk of recurrent stone formation was consistently higher, in those patients who consume more animal protein, oxalate containing vegetables like tomatoes and also in patients who consume alcohol frequently. However in this study the differences were found to be not statistically significant (p>0.05), (Table 5).

Graph 1: Age wise distribution (%)

Graph 2: Past history of renal stone disease (%)

Graph 3: Diagnostic method of recurrent renal stone disease (%)

Graph 4: Treatment used for renal stone disease (%)

Table 1: Gender wise comparison of lab serum parameters

Table 2: Evaluation of two random 24-hour urine samples

Table 3: Analysis of renal stones

Table 4: Association between medication history and recurrent renal stones

Table 5: Association between dietary history and recurrent renal stones

This prospective study was done on 50 recurrent stone formers and a detailed evaluation of the serum and urinary parameters including clinical characteristics was performed.The majority of the study participants with recurrent renal stone formation belonged to the 2nd, 3rd and 4th decades of life (24%, 30%, and 22% respectively) in the present study. It was also observed that the rate of recurrent stone formation was slightly higher in more than 60 years age group compared to patients in 15-20 years age group (4% and 2%).

Meyers A.M et al^[8] in their review studyreported that the percentage change in the incidence of recurrent renal stones was found to be higher in the younger age group (10 – 19 years) with 23% incidence followed by 16% in the 3rd and 4th decades which were congruent with the observations made in the present study.The results from the study revealed that the greatest increase in the incidence of renal stone formation was among 15 – 19 year age group (incidence ratio 1.26). The authors concluded that there is doubling risk of nephrolithiasis during childhood.A long term epidemiologic study done by Johnson CM et al ^[9] over a period of 25 years revealed that, stone formation peaks at 4th and 6th decades of life, however in the present study formation of recurrent renal stones was observed to be higher in the 3rd and 4th decades of life.

Most of the patients in the present study were men (70%) and only 15 (30%) patients are women. Bihl G et al^[10] in their study on recurrent renal stone disease also reported a higher incidence in males (12%) compared to females (5%). Gregory E. Tasian et al ^[11] observed a converse relationship of increased incidence of nephrolithiasis in women.

Evidence from several studies, reported a high recurrence rate of renal stones with almost as high as 50%. Similarly in a review study done by Skolarikos A et al^[12] estimated that the recurrence rate after initial stone formation was 50% at 5 years and 80-90% at 10 years. In the present study, as many as 66% of the patients had a past history of renal stone formation between 1 to 5 years and 14% had a duration of more than 5 years.

Pain at the renal angle and abdomen was the most common presenting complaint by many (31.9%) of the patients, other clinical features observed were, dysuria in 23.1% of the patients, hematuria in 20.9%, fever in 12.1%, vomiting in 9.9% and 2.2% of the patients presented with increased frequency of micturition or incontinence. Parmar MS et al^[12] in their clinical review on renal stones also stated that the classic presentation of pain associated with renal stones is colicky in nature.

In a study done by Eskelinen M et al ^[13] colicky pain with loin to groin distribution, combined with tenderness at the renal angle and microscopic hematuria were reported as highly predictive of stone disease and the sensitivity was reported to be 84% with a specificity of 99%. Similar clinical presentation was observed in the present study with majority patients complaining pain as the predominant symptom, however hematuria was reported by only 20.9% of the patients.

A urinary pH > 7.5 was suggested as a bacterial infection with urease production, while pH < 5.5 was stated to be indicative of uric acid calculi. A 24 hour urine collection for volume and other metabolic testing is advised by a number of researchers, for recurrent stone formers.

Renal Ultrasonography was recommended by several studies to establish hydronephrosis and to detect large renal stones. It is also useful to measure resistive index.In the present study all the patients were diagnosed using an ultrasonogram.Although plain x-ray abdomen (KUB) is useful for identifying several stones, 10% to 20% of the radiolucent renal calculi can be missed.The combined use of USG and X-ray KUB helped to detect stones in 22% of the patients in the present study. Thungkatikajonkit P et al^[13] in their study reported that combining renal USG and KUB is a very cost effective alternative to CT scans. It was demonstrated that, the combined use of USG and X-ray KUB has a diagnostic accuracy of 90%, sensitivity of 88% and a specificity of 93%. Though most of the recurrent stones could be diagnosed with USG+Xray KUB in the present study also, NCCT was done in most of the patients to plan management.

Urine culture done in the present study revealed that most of the samples had no evidence of bacterial growth (82%). Presence of E.coli was seen in 8% of the samples and proteus was isolated in the remaining 10%.

In the present study, hyperuricosuria was detected in 18% of the patients and the mean serum uric acid levels were 5.19 mg/dl. Hypercalcemia was evident in 24% of the patients, who had a mean serum calcium levels of 9.33 mg/dl. Erdamar H et al^[14] in their study reported that the levels of calcium and sodium are significantly higher in patients with recurrent renal calculi. Hosseini et al^[15] in their comparative study between first-episode of nephrolithiasis with recurrent cases reported that the most common metabolic abnormalities were hypercalcemia (11%) and hyperuricemia (14%), which were almost congruent with the findings observed in the present study.

A 24 hour urine collection in patients is recommended as an important investigative modality for a comprehensive metabolic evaluation by many studies. The CUA and other professional organizations currently recommend performing two consecutive 24 urine collections for metabolic evaluation of the patients with nephrolithiasis ^[15]It was also reported that upto 45% of the patients will show significant differences between the two 24 hour urine samples. The present study revealed that the volume of urine was low in 36% of the patients in the first sample and in the consecutive sample it was reduced to 12% with a statistical significance of (p<0.05). Similar statistically significant differences were noted between creatinine, calcium and oxalate (p<0.05). However there is no significant difference observed between urinary parameters like, pH, phosphate, uric acid, citrate and sodium (p>0.05).Hosseini et al^[16] in their study reported that most of the patients had decreased urine output which was less than 1 lit per day (24%) similar to the findings observed in the present study.

Hypercalciuria was seen in 36% of the patients in the initial urine sample and it was reduced to 18% in the consecutive sample with a statistically significant difference in the present study (p<0.05).Curhan GC et al^[17] also reported hypercalciuria as the most common metabolic abnormality occurring, with a higher rate seen among women (38%) compared to men (35%).Ha YS et al^[18] in their study reported phosphaturia as a promising predictor of recurrent stone formation in patients with urolithiasis. However in the present study hyperphosphaturia was found to be not significant (p>0.05).

Mittal RD et al ^[19] in their study on risk factors for renal stone formation reported that the most common metabolic abnormalities observed were hypocitraturia and hyperoxalauria. In their study 46% of the patients had hypercalciuria and 40% of the patients had hypocitraturia. However in the present study hypocitraturia was found to be not significant, but hypercalciuria was found to be significantly associated with recurrent stone formation.

Fontenelle LF et al ^[19] in their review on the treatment and prevention of renal stones stated that most common component of kidney stones is calciumeither calcium oxalate or phosphate. Congruent findings are observed in the present study with most of the stones being composed of calcium oxalate (43%), calcium carbonate (29%) and calcium phosphate (14%).Fontenelle LF et al also mentioned that uric acid stones may occur in the ranges between 3 – 16 %, similar to these figures 14% of the patients were found to have uric acid stones in the present study.

In the present study a statistically significant difference was observed (p<0.05) with higher number of patients (63.3%) using any drugs were found to have recurrent stone formation compared to those who are not using any kind of medication (36.7%).When different dietary factors are analyzed to find out the risk of recurrent stone formation, the results from the present study revealed that less water consumption of only 2-3 L, excessive salt intake were found to be statistically significantly associated (p<0.05).Ferraro et al ^[20] in their study described that potential stone risk is increased by the dietary factors such as reduction in the fluid intake, increase in sodium intake,calcium intake and meat intake, Reduction in fruit intake and increased intake of dietary content with high oxalate levels, which are similar to the results obtained in the present study.

The characteristic clinical presentation in most of the patients is colicky pain with loin to groin distribution, combined with tenderness at the renal angle and microscopic haematuria.The combined use of USG and X-ray KUB a very cost effective alternative to CT scans for diagnosis but for management CT scan is superior.Hypercalcemia, hyperuricemia,hypocitraturia and elevated serum sodium levels are highly suggestive of Nephrolithiasis.24 hour urine collection in patients is recommended as an important investigative modality for a comprehensive metabolic evaluation. The chemical composition of most of the stones is found to be calcium oxalate and the other component found in the present study was uric acid. Prevention plays a key role in the management of recurrent stones.

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