Cystine Stone Patients Research Articles

Challenges in diagnosis and treatment of cystinuria patients with Urolithiasis: multicenter patient centered study.

Cystinuria represents a rare cause of urolithiasis, accounting for 1% of all cases. However, it poses unique challenges in diagnosis and management. This study aimed to examine the challenges of managing cystine stones from the perspective of cystinuria patients. Following ethical approval, we reviewed the medical records of cystine stone patients treated at four tertiary centers from 2016 to 2021 and surveyed them on their perceptions of cystinuria. It included questions about demographic characteristics, herbal treatments, pain management, online engagement, disease outcomes, and cystinuria-related fears. The study included 28 adults with cystinuria nephrolithiasis, with a mean age of 30.5 years. Of these, 78.6% had consanguineous parents, and the first stone episode occurred at a mean of 14.82 years age. Family history of Cystinuria was encountered in 82.1%. Cystinuria was diagnosed after a mean of 6.43 years from the first stone episode, and stone analysis was performed in 22/28 after a mean of 3.86 years from the first stone episode. Only 17 patients (60.8%) underwent metabolic evaluation for kidney stones. Regarding non-surgical treatments, 13 (46.5%) patients received alkalinization medication, and only 10 (35.7%) were prescribed chelating agent therapy. Additionally, 50% of patients took herbal remedies. The diagnosis of cystinuria is often delayed, leading to a delay in receiving medical treatment (alkalinization and chelating agents) and poor health education and counseling. Thus, referring cystinuria patients to tertiary hospitals and providing a multidisciplinary approach might decrease the morbidity of the disease and enhance their well-being.

Outcomes and Long-term Follow-up of Patients with Cystine Stones: a Systematic Review.

Cystine stone patients can be difficult to manage with frequent recurrences. We performed a systematic review with a view to assessing interventions, compliance and their long-term outcomes. Ten retrospective observational studies (253 patients) assessed the outcomes and long-term follow-up of cystine stone patients. The mean length of follow-up was 9.6years (range 3.5-21.8years). The overall mean number of surgical procedures/patient was 5.7 (range 2-9.8/patient) with the overall mean number of surgical procedures/patient/year at 0.59 (range 0.22-1.32/patient/year). While open surgery has decreased over the last decade and PCNL has been stable, there seems to be a rise of RIRS during this period. Patients with cystine stones need periodic interventions for stone recurrences despite medical management, with limited data showing the impact on renal function. While the management is individualised, wide variability exists with often poor and incomplete patient data.

Protective effect of salvianolic acid B against oxidative injury associated with cystine stone formation

The aim of this study was to investigate the role of oxidative stress in cystine crystal formation and whether salvianolic acid B, a natural antioxidant, could prevent cystine-mediated oxidative injury in vivo and in vitro. The levels of oxidative stress and antioxidase activity in cystine stone patients were assessed. Then, the oxidative stress exerted by cystine on human kidney-2 (HK-2) cell viability and biochemical parameters including antioxidase activity and antioxidant protein expression were evaluated, and the protective action of salvianolic acid B was also examined. Finally, salvianolic acid B was tested to determine whether it could prevent or reduce renal crystal formation in Slc7a9 knockout mice. The activity levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were decreased, and the amount of malondialdehyde (MDA) was increased in patients with cystine stones compared with people without cystine stones (p < 0.05). Significant reductions in cell viability, antioxidase activity and antioxidant protein expression levels were found in the cystine group compared with controls. However, such oxidative injuries were prevented by salvianolic acid B. In the animal study, loose crystals with white spots were seen in the renal parenchyma, bilateral renal pelvis and bladders in the Slc7a9 knockout group. In contrast, no renal crystals were seen in the control group, and markedly fewer crystals with significantly higher antioxidase activity and diminished oxidative stress were detected in the salvianolic acid B group. Cystine cytotoxicity in vitro and cystine stone formation in vivo were associated with oxidative stress, and salvianolic acid B could protect against cystine stone-induced injury.

Clinical Outcomes for Cystinuria Patients with Unilateral Versus Bilateral Cystine Stone Disease.

Cystinuria is a genetic disorder marked by elevated urinary cystine excretion and recurrent cystine nephrolithiasis. Interestingly, despite seemingly similar contralateral renal anatomy, a subset of cystinuric patients consistently form stones in only one kidney. The aim of this study is to evaluate clinical outcomes in unilateral vs bilateral cystine stone formers. We performed a retrospective case-control study of cystinuric patients evaluated and treated at the University of California, San Francisco between 1994 and 2015 and categorized patients as either unilateral or bilateral stone formers. Clinical presentation, baseline patient demographics, stone procedures, medical therapy regimens, and long-term renal function were compared between the two groups. A total of 42 cystine stone patients (22 female, 20 male) were included in the analysis. The median age at first presentation was 18.5 years and median age at study conclusion was 45.5 years. Two-thirds of patients (n = 28) had a history of bilateral stones, whereas one-third (n = 14) had unilateral stones. Medical therapy regimens were similar between groups. Despite an increased average number of lifetime surgeries (7.5 sessions for bilateral vs 3.7 sessions for unilateral, p < 0.05), there was no significant difference in medians of the most recent glomerular filtration rate when compared with unilateral stone formers (81.5 vs 95 mL/min, respectively; p = 0.28). The majority of cystinuric patients within our cohort form stones bilaterally during their lifetime, and require more surgical interventions than unilateral stone formers. Despite this, overall renal function is well preserved in unilateral and bilateral cystinuric stone formers treated with minimally invasive stone extraction procedures.

Clinical and genetic characterization of Chinese pediatric cystine stone patients

Cystine stone is the only clinical manifestation in patients with cystinuria, which is an autosomal recessive inheritable disease. However, clinical and genetic data vary among patients in different countries. To investigate the characteristics of Chinese pediatric cystine stone patients. Thirteen pediatric patients with cystine stones were evaluated in our clinic between 2012 and 2015. Gene mutations in SLC3A1 and SLC7A9 were investigated. Metabolic evaluation was also performed. Thirteen pediatric patients with calcium oxalate stones were selected as controls. Of these patients, eight were males and five were females. Average age at detection of the first stone was 6.8±5.2 years. Urinary stones in three of the 13 cystine patients were composed of cystine and calcium oxalate. The 63.6% of patients with upper urinary stones had bilateral stones. A total of 17 different missense mutations were identified, and 12 of these mutations were first reported in this study. Metabolic abnormalities could be detected in 77% of cystine stone patients. The most common metabolic abnormality was hyperoxaluria, followed by hypercalciuria and hypocitraturia. Compared with calcium stone patients, our cystine stone patients had a higher rate of bilateral stones, larger stone size, higher levels of serum BUN and Cr, urine citrate excretion (Table), and higher mean value of surgeries per patient. By contrast, the opposite was true for urine oxalate excretion and AP (CaOx) index EQ. The urine excretion of cystine was not correlated with other urinary constituents. Patients with cystinuria frequently suffer recurrent renal stones and may subsequently need a series of stone removal procedures during their lifetime. This condition is likely to affect their overall renal function. SLC3A1 and SLC7A9 have been extensively investigated, but a detection rate of 100% in cystinuric patients has yet to be obtained. In our study, we found 14 missense mutations in 18 of 26 alleles except four mutation polymorphisms. Most of the gene mutations found in our study were their first reports. Metabolic abnormalities were frequently found in cystine stone patients, but their risk of calcium oxalate stone formation was relatively lower than that of patients with calcium oxalate stones. Cystine stone patients are at risk of impaired renal function and the formation of calcium oxalate stones. Most of the gene mutations identified in our patients were first reported in this study. Therefore, cystinuria possibly exhibits genetic and allelic heterogeneity in Chinese pediatric cystine stone patients.

The challenge of cystine and struvite stone formers: clinical, metabolic and surgical assessment.

ABSTRACTPurpose:To compare the clinical, metabolic, and calculi characteristics of cystine and struvite stone patients after percutaneous nephrolithotripsy (PCNL).Material and Methods:Between January/2006-July/2013, 11 cystine stone patients were treated in our clinic. Of those, 3 were excluded due to incomplete follow-up. Eight cystine stone patients (2 with bilateral disease; 10 renal units-RU) were considered for further analysis. A cohort of 8 struvite stone formers (10RU) was matched having the same age, gender, body mass index (BMI) and Guys stone score. Analyzed parameters comprised demographic data, serum/urinary metabolic evaluation and surgical outcomes.Results:Both groups had 6 female patients. Groups were similar in regards to age, gender, BMI, stone burden, and serum creatinine (p=NS). All patients had PCNL as the first surgical treatment modality. Stone free rate (SFR) after the first PCNL tended to be lower (0%) in the cystine compared to the struvite group (40%)(p=0.08). Final SFR after secondary procedures increased to 70% in cystine and 80% in struvite patients (p=1.0); mean number of procedures to achieve stone free status was higher in the first group (3.57 vs. 2.0;p=0.028). Hypocitraturia was found in all patients, but struvite cases presented with lower mean urinary citrate levels (p=0.016). Other common abnormalities were elevated urinary pH (cystine 75% and struvite 62.5%;p=1.0) and low urinary volume (62.5%,37.5%;p=0.63).Conclusion:Multiple interventions and suboptimal stone free rates are trait of the significant stone burden of struvite and cystine patients. Underlying metabolic abnormalities characterized by increased urinary pH, hypocitraturia and low urinary volume are often encountered in both populations.

E106 Retrograde intrarenal surgery is a safe technique for pediatric cystine stone patients

E106 Retrograde intrarenal surgery is a safe technique for pediatric cystine stone patients

Comparison of renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China

To compare renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China. Between 2008 and 2011, thirty cystine stone patients were involved in our study, and an equal number of age- and gender pair-matched patients with calcium oxalate stones. Non-stone forming individuals were elected as controls. The evaluation included blood chemistry studies and 24-h urine collection in both groups of patients. The cystine stone patients had higher mean values of serum blood urea nitrogen, urate and creatinine levels than patients in other two groups. With respect to urine risk factors, cystine stone patients had higher urinary citrate and lower urinary oxalate and creatinine than calcium oxalate stone patients. When compared to non-stone forming individuals, cystine stone patients had higher urinary urate excretion and lower urinary creatinine excretion. Metabolic abnormalities could be demonstrated in 80 % of the cystine stone patients and in 100 % of the calcium oxalate stone patients. We also compared urine risk factors among cystine stone patients with different urine cystine excretion (<1 mmol/24 h, 1-2 mmol/24 h and >2 mmol/24 h). No significant difference was found in urine risk factors among three groups. This study suggested that cystine stone patients were at greater risk for the loss of renal function than calcium oxalate stone patients, but the risk of the formation of calcium oxalate stones was lower. Our results also indicated that urinary cystine had little or no impact on the excretion of urine chemistries in cystine stone patients.

Etracorporeal Shock Wave Lithotripsy (ESWL) によるシスチン結石の治療経験

Thirty patients (16 men and 14 women) with cystine urinary stones were treated by extracorporeal shock wave lithotripsy (Dormer HM-3) from December 1984 through October 1989. The average patient age was 35.2 years with a range of 14 to 59 years. Seventy per cent of these subjects had had previous open surgical operations for stones. The cases consisted of 7 ureteral stones and 37 renal stones, including 15 staghorn calculi. An average of 1.3 session of ESWL was carried out to treat ureteral stones. Thirty-seven renal units with renal stone required 96 sessions of lithotripsy (average 2.6 sessions per unit). Seven patients with ureteral stones required auxiliary procedures, i.e., one transurethral lithotripsy (TUL), two percutaneous nephrostomies (PNS) and one open surgery. Thirty-seven renal stones, including staghorn calculi was treated by ESWL and auxiliary treatment of 21 TUL procedures, one PNS, 16 PNL procedures and one chemical chemolysis. Successful fragmentation (residual debris less than or equal to 4 mm) was achieved in 85.7% of ureteral stones, 90.9% of renal stones and 73.3% of staghorn calculi. The stone free rates of patients with ureteral stones, renal stones and staghorn calculi were 71.4%, 50.0% and 53.5%, respectively, at 3 months after ESWL. No serious complications were seen in this series. Fever above 38.5 degrees C was the most common complications (13.5%). Ureteral perforation was encountered once in TUL procedures. Transfusion and selective arterial embolization were needed for one case treated by PNL procedures. Although cystine stone is harder to be fragmented by ESWL than other stone composition, ESWL and endourology may be effective and safe procedures for cystine stone patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-Term Observation of Young Cystinuric Patients under Ascorbic Acid Therapy

Long-term results of ascorbic acid monotherapy in four young patients with cystine stone complaints are reported. The therapeutic program is based on the descriptions by Asper and Schmucki, who publicized the method for the first time in 1979. Clinical course observations, renal function checks as well as the excretion of cystine, uric acid and oxalic acid during ascorbic acid therapy of our patient pool will be discussed. Clinical observations made to date indicate that ascorbic acid therapy is a practical, inexpensive prophylaxis for cystine stone patients that is virtually free of side effects.