In a new study of patients with chronic kidney disease, the presence of kidney stones, compared with their absence, was significantly associated with a 2.3-fold increased risk of osteoporotic fracture

Kidney stones predict an increased risk of osteoporotic fracture in patients with chronic kidney disease (CKD), new data suggest.

“Despite previous reports that kidney stones were associated with higher risk of osteoporotic fracture, the association of kidney stones and osteoporotic fracture has not been established in patients with CKD … Our findings suggest that the presence of kidney stones should be considered as a clinical risk factor for osteoporotic fracture in patients with CKD,” investigators wrote in Scientific Reports.

A team led by Dong Ho Shin, MD, of Hallym University, Kandong Sacred Heart Hospital, Seoul, Korea, conducted a retrospective medical record-based study that included 2282 patients with stable stage 3–4 CKD who were treated from 2007 to 2017. Kidney stones developed in 113 patients. Investigators propensity score matched these patients with 113 patients without kidney stones.

During a mean follow-up period of 64.7 months, osteoporotic fractures occurred more frequently in patients with than without kidney stones (29.2% vs 14.2%). After adjusting for age, sex, body mass index, and other potential confounders, kidney stones were significantly associated with a 2.3-fold increased risk of osteoporotic fracture.

The authors acknowledged study limitations. Their study was retrospective, conducted at a single center, and based on a small number of CKD patients with kidney stones. In addition, they did not measure bone mineral density with dual-energy X-ray absorptiometry.

References

Han SG, Oh J, Jeon HJ, et al. Kidney stones and risk of osteoporotic fracture in chronic kidney disease. Sci Rep. 2019;9(1):1929. Published online ahead of print.

Approximately one‐third of patients with gout had kidney stones, more than half of whom had bilateral and multiple stones. Photo Credit: Scott Camazine

Laterality, assessed using unenhanced computed tomography (CT) in patients with gout, may be useful to help characterize the presence of nephrolithiasis, according to results from a study published in the International Journal of Rheumatic Diseases.

Researchers conducted a cross-sectional study of 350 men with acute gout, defined according to the American College of Rheumatology 1977 criteria. The group of patients underwent helical CT imaging and were assessed for the presence of renal calculi. The investigators divided the patients into 3 separate groups: unilateral, bilateral, and non-stone carriers. The links between nephrolithiasis and renal function, serum urate level, and uric acid metabolism were examined in these patients.

After statistical analysis, the researchers identified renal calculi in 108 (31%) study participants, which included 50 and 58 patients in the unilateral and bilateral groups, respectively. In addition, they found that 59% of these patients had no prior history of urolithiasis.  

The investigators also reported that serum creatinine, serum urate, and uric acid metabolism (P <.001, P =.001, P =.043, respectively) were significantly increased, while estimated glomerular filtration rate (P =.039) was significantly decreased in the bilateral group vs the non-stone group.

“There have been no previous reports on the laterality of nephrolithiasis in gout. The present investigation clarified that more than half of all gout patients with kidney stone(s) were bilateral and multiple stone carriers,” the researchers wrote.

“More studies will be required for better identification of the CT features of nephrolithiasis,” they concluded.

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Reference

Shimizu T, Hori H, Umeyama M, Shimizu K. Characteristics of gout patients according to the laterality of nephrolithiasis: A cross-sectional study using helical computed tomography [published online November 28, 2018]. Int J Rheum Dis. doi: 10.1111/1756-185X.13443

Kidney stones are associated with an increased risk of papillary renal cell carcinoma and upper tract urothelial carcinoma.

Kidney stones are associated with an increased risk of papillary renal cell carcinoma (RCC) and upper tract urothelial carcinoma (UTUC), according to investigators.

In a study of 120,852 participants in the prospective Netherlands Cohort Study (NLCS), Jeroen A.A. van de Pol, and colleagues at Maastricht University in Maastricht, The Netherlands, found that individuals who reported a history of kidney stones had a significant 39% greater risk of RCC overall compared with those who did not, after adjusting for multiple variables, van de Pol’s team reported in the British Journal of Cancer. When the investigators examined the association by RCC type, they found that a history of kidney stones was associated with a significant 3-fold increased risk of papillary RCC (pRCC), but was not significantly associated with clear-cell RCC (ccRCC).

“We hypothesize that the difference in risk between these RCC subtypes may be rather due to differences in metabolism between these cancer subtypes rather than a direct effect from the kidney stones,” van de Pol told Renal & Urology News. “Potentially, these RCC subtypes are affected by a lifestyle that is related to kidney stone formation. In our study, we have taken multiple risk factors into account, such as alcohol usage, hypertension and obesity, but it might be that other factors also affect both the risk of developing a kidney stone and the risk of developing RCC.”

The investigators said the study, to their knowledge, is the first to find an increased pRCC risk among individuals with kidney stones.

Kidney stone history was associated with a significant 1.7-fold increased risk of UTUC. The study found no difference between localization of tumors in the renal pelvis or ureter. “In contrast to the proximal tubule, stone formation is common in the renal pelvis and ureter, which enables kidney stones to cause chronic irritation and inflammation to urethelial cells,” the authors explained. “In turn, this may explain the increased UTUC risk in relation to kidney stones.”

In addition, results showed that younger age at kidney stone diagnosis was a risk factor for RCC overall. A diagnosis of kidney stones among individuals younger than 40 years was associated with a significant 2-fold greater overall risk of RCC compared with those diagnosed later.

The study, which focused on a subcohort of 4352 NLCS participants, also identified sex disparities in the association between stone history and RCC. Among men, a history of kidney stones, compared with no history, was associated with a significant 1.42-fold greater overall risk of RCC and 2.4-fold greater risk of pRCC, but was not associated with ccRCC. Among women, kidney stone history was associated with a significant 16.4-fold increased risk of pRCC, but was not significantly associated with the risk of RCC overall or ccRCC risk. The number of women who developed pRCC was limited in this study, however.

The NLCS was a prospective study initiated in 1986 to investigate the association between diet and cancer. At baseline, all participants completed a self-administered questionnaire on diet, medical conditions, and other risk factors for cancer. Of the 4352 subcohort members, 365 (8.4%) had a history of kidney stones and 3987 (91.6%) did not. During 20.3 years of follow-up, 544 RCC cases and 140 UTUC cases developed in the full cohort.

In a previous meta-analysis published in QJM (2015;108:205-212), a team led by Wisit Cheungpasitporn, MD, now with the University of Mississippi Medical Center in Jackson, found that a history of kidney stones was associated with a significant 76% increased of RCC overall. A subgroup analysis, however, revealed that a history of kidney stones increased RCC risk only in men.

Commenting on the new study, Dr Cheungpasitporn noted that one of its major strengths was the available data on the differentiation between histologic subtypes of RCC, which provide novel information that builds on the findings of the meta-analysis by his team. Another strength was the extensive adjustment of hazard ratios for potential confounding factors known to be related to kidney cancer, including age, sex, body mass index, smoking status, and hypertension. “The investigators successfully demonstrated that kidney stones were associated with increased papillary RCC risk, but not ccRCC risk,” Dr Cheungpasitporn said.

He pointed out that the new study had limited data on kidney stone composition, urinary supersaturation, family history of kidney cancer, and occupational and other exposures shown to be associated with kidney cancer. In addition, previous studies have shown the link between kidney stones and kidney cancer may be subject to surveillance bias, as patients with kidney stones would be more likely to have follow-up imaging studies. Thus, patients with kidney stones are more likely than individuals without kidney stones to have kidney cancer detected.

“Despite these limitations, the findings from this well-conducted, large population-based study from the Netherlands Cohort Study confirmed the association of kidney stones with kidney cancer that we demonstrated in our previous meta-analysis,” Dr Cheungpasitporn said. “Thus, future studies are required to identify if there is any role in term of public health or early prevention of cancer in patients with kidney stones. Moreover, future studies are required to provide additional insight on the mechanisms underlying this association.”

Reference

Van de Pol JAA, van den Brandt PA, Schouten LJ. Kidney stones and risk of renal cell carcinoma and upper tract urothelial carcinoma: the Netherlands Cohort Study. Br J Cancer. 2018; published online ahead of print.

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Myocardial infarction following the kidney stone procedure is twice as likely among patients with 3 to 4 components of metabolic syndrome vs no components, a study found.

Patients with metabolic syndrome (MetS) are at higher risk of myocardial infarction after undergoing percutaneous nephrolithotomy (PCNL), according to a new study.

“Routine preoperative cardiac testing may benefit this population before PCNL,” investigators concluded in a paper published in the Journal of Endourology.

MetS is a constellation of conditions, including hypertension, diabetes mellitus, dyslipidemia, and obesity.

Using the Healthcare Cost and Utilization Project State Inpatient Database for Florida and California, Carrie E. Johans, MD, of Loyola University Medical Center in Maywood, Illinois, and colleagues identified 39,868 patients who underwent percutaneous nephrolithotomy for upper urinary tract stones. Of these, 19,268 (48.3%) and 2668 (6.7%) had 1–2 and 3–4 MetS conditions, respectively. The remaining 17,932 (45%) had no MetS conditions.

The incidence of postoperative myocardial infarction (MI) increased from 0.6% of patients with no MetS conditions, 1.0% of those with 1–2 MetS conditions, and 1.8% of those with 3–4 MetS conditions, Dr Johans’ team reported.

On multivariate analysis, patients with 3–4 MetS conditions had significant 2.2-fold increased odds of postoperative MI compared with those who had no MetS conditions. The odds of MI were not significantly increased among patients with 1–2 MetS conditions.

Reference

Johans CE, Bajic P, Kirshenbaum E, et al. Metabolic syndrome increases risk of postoperative myocardial infarction following percutaneous nephrolithotomy. J Endourol. 2018; published online ahead of print.

Development of kidney stones is 6.2 times more likely among patients with persistent hyponatremia than those without a history of hyponatremia.

Recent and persistent hyponatremia are associated with an increased risk of kidney stones, according to investigators.

Naoto Tominaga, MD, PhD, of Georgetown University Medical Center in Washington, D.C., and colleagues compared 20,199 patients with kidney stones (cases) and 20,199 patients without kidney stones (controls) matched by age, sex, race, and encounter window. Compared with patients without a history of hyponatremia, those with recent and persistent hyponatremia had significant 2.0- and 6.2-fold increased odds of kidney stones, respectively, Dr Tominaga’s team reported online in PLOS One.

Based on prior research findings, Dr Tominaga’s team stated that increased urine calcium excretion is a potential common link between hyponatremia and kidney stones.

The study is the first to demonstrate an association between hyponatremia and kidney stones in a large US health system, according to the researchers.

The investigators analyzed patient data extracted from the MedStar Health system database, which contained more than 3.4 million unique patient records as of March 2016. Cases and controls had a mean age of 43.6 years. The groups were 48.7% female and 61.4% white. The mean encounter window was 1304 days.

Patients considered to have recent hyponatremia had at least 1 serum sodium level of less than 135 mEq/L within 30 days before the end of the encounter window. Patients classified as having persistent hyponatremia had at least 1 serum sodium level of less than 135 mEq/L within 30 days before the end of the encounter window and at least 2 serum sodium measurements of less than 135 mEq/L at least 1 year apart until 30 days before the end of the encounter window during the encounter window.

Reference

Tominaga N, Fernandez SJ, Mete M, et al. Hyponatremia and the risk of kidney stones: A matched case-control study in a large US health system. PLoS One. 2018;13(9):e0203942.

Percutaneous nephrostomy is associated with a higher spontaneous stone passage rate than retrograde ureteral stents in patients with hydronephrosis due to ureteric stones

Percutaneous nephrostomy (PCN) is associated with a higher spontaneous stone passage rate compared with retrograde ureteral stent (RUS) placement in patients with hydronephrosis secondary to ureteric stones, a new study suggests. PCN also is better tolerated and associated with fewer urinary symptoms, according to investigators.

Nuno de Sousa Morais, MD, of Hospital de Braga in Braga, Portugal, and colleagues conducted a prospective trial that included 50 patients with hydronephrosis secondary to ureteral stones who required urgent urinary diversion. The investigators selected 18 for PCN and 32 for RUS placement. The PCN group had a larger stone size than the RUS group (median 92 vs 47 mm²).

The spontaneous stone passage (SSP) rate was higher in the PCN arm (38.9% vs 25%), Dr Morais’ team reported online ahead of print in Urolithiasis. On multivariable analysis, PCN was associated with significantly greater odds of SSP compared with RUS, after adjusting for stone location, size, and previous ureteral manipulation and expulsive therapy.

In addition, 30.2% of stones had an upward displacement associated with retrograde endoscopy, the investigators reported. They observed a significant decrease in pre- and post-intervention quality of life in the RUS group, but not in the PCN group.

Patients in the RUS group had more urinary symptoms than the PCN group, mostly hematuria (68.7% vs 16.7%) and dysuria (78.3% vs 16.7%).

Reference

De Sousa Morais N, Pereira JP, Mota P, et al. Percutaneous nephrostomy vs ureteral stent for hydronephrosis secondary to ureteric calculi: impact on spontaneous stone passage and health-related quality of life—a prospective study. Urolithiasis. 2018; published online ahead of print.

Low ureteral wall thickness is associated with a greater likelihood of spontaneous passage of ureteral stones 10 mm or less in diameter, according to a new study.

Ureteral wall thickness (UWT) may be useful for predicting spontaneous passage (SP) of small ureteral stones, according to a preliminary report from investigators in Japan.

A retrospective study of 418 patients with uncomplicated ureteral stones no larger than 10 mm in maximum diameter demonstrated that low UWT was associated with a significantly greater 4-week SP rate than a high UWT (76.4% vs 14.7%), Takashi Yoshida, MD, and colleagues at Kansai Medical University in Osaka, and colleagues reported online ahead of print in the World Journal of Urology. Non-contrast computed tomography was used to measure UWT at the point of greatest soft-tissue thickness around the circumference of a stone.

In addition, high UWT was associated with a significantly greater risk of stone-related complications (SRCs) within 4 weeks compared with low UWT (16.4% vs 7.2%).

Receiver operator curve analysis revealed that 2.71 mm was the optimal cut-off value for UWT, with a predictive accuracy of 0.83. Combining UWT with traditional factors such as stone location and size increased the predictive accuracy of SP to up to 0.90.

 “These findings suggest that UWT might improve our clinical decision-making at the initial visit regarding whether patients with ureteral stones can be conservatively treated or must undergo immediate interventions,” the authors wrote. “To the best of our knowledge, this is the first report to present the clinical significance of UWT in terms of predicting SP of uncomplicated ureteral stones.”

In a previous study published in Urology, Dr Yoshida and colleagues noted, they demonstrated that increased UWT was significantly associated with the presence of stone impaction as well as poor endoscopic findings such as ureteral edema, polyps, ischemic mucosa, and stone fixation in the ureter.

“Therefore, we believe UWT measurement can be a surrogate marker for the presence of stone impaction and a significant factor for predicting SP as well as SRCs secondary to stone impaction.”

In a discussion of study limitations, the investigators pointed out that their study was a retrospective analysis of a relatively small cohort from a single institution.

References

Yoshida T, Inoue T, Omura N, et al. Ureteral wall thickness as a preoperative indicator of impacted stones in patients with ureteral stones undergoing ureteroscopic lithotripsy. Urology. 2017;106:45-49.

Recurrent kidney stone formers are at higher risk of end-stage renal disease than patients who form incident symptomatic stones, study finds.

Patients who have recurrent symptomatic kidney stones are at higher risk of end-stage renal disease (ESRD) than those who experience incident symptomatic kidney stones, investigators concluded. In addition, patients with asymptomatic stones and bladder stone formers have an increased all-cause mortality risk than non-stone formers.

“Recurrent stone formers might accrue incremental kidney injury with each stone event,” a research team led by Andrew D. Rule, MD, of Mayo Clinic in Rochester, Minnesota, reported online ahead of print in the American Journal of Kidney Diseases. “Therefore, treatments to prevent kidney stone recurrence may be beneficial for delaying CKD [chronic kidney disease] progression, especially because kidney stone events are associated with reductions in glomerular filtration rates and increases in proteinuria.”

Dr Rule and his collaborators conducted a historical matched-cohort study that included 6,984 stone formers and 28,044 non-stone formers matched by age and sex. All were residents of Olmsted County, Minnesota. Investigators used ICD-9 codes to identify residents’ first documented urinary stones in the county from January 1, 1984 to December 31, 2012.

Following a review of medical charts, the investigators categorized subjects into 5 mutually exclusive categories: incident symptomatic kidney (first stone event during the study period), recurrent symptomatic kidney (first stone event occurred before 1984 or residency in Olmsted County with recurrence in Olmsted County during the study period), asymptomatic kidney stone only (incidentally detected), bladder stone only, and miscoded (no urinary stone).

Over a mean follow-up of 12 years, ESRD developed in 65 stone formers (0.93%) and 102 non-stone formers (0.36%), Dr Rule’s team reported. Compared with non-stone formers, recurrent symptomatic kidney, asymptomatic kidney, and miscoded stone formers had a significant 2.3-fold, 3.9-fold, and 6.1-fold increased risk of ESRD, respectively, after adjusting for baseline diabetes, hypertension, chronic kidney disease, dyslipidemia, gout, and obesity. The investigators observed no increased ESRD risk among incident symptomatic kidney and bladder stone formers. They identified ESRD events (initiation of maintenance dialysis or kidney transplantation) using the US Renal Data System database.

 “The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggest that stone events are associated with kidney injury,” the authors concluded.

In addition, asymptomatic kidney stone formers and bladder stone formers had a significant 40% and 37% increased risk of all-cause mortality risk, respectively, compared with non-stone formers.

Dr Rule’s team reported that “asymptomatic kidney stone formers and miscoded stone formers have underlying medical conditions such as urinary tract infections, cancers, and gastrointestinal diseases that led to incidental detection of kidney stones with imaging or were misdiagnosed as kidney stones. These medical conditions, rather than kidney stones, likely explain the increased risk for ESRD or mortality.”

According to the investigators, the study demonstrated the value of careful chart validation when studying kidney stone disease rather than relying on administrative codes.

Dr Rule and his collaborators also evaluated cause-specific mortality using underlying diagnoses on patients’ death certificates and found that 300 stone formers (4.3%) and 899 non-stone formers (3.2%) had deaths attributed to cancer. The risk of cancer mortality was higher among incident symptomatic kidney stone formers and bladder stone formers.

“The exact mechanism driving the higher risk for cancer mortality in stone formers is unclear,” the authors wrote. “One speculative pathogenic mechanism is that local irritation and inflammation contribute to chronic systemic inflammation and cytokine release, which promote tumorigenesis.”

Reference

Dhondup T, Kittanamongkolchai W, Waughan LE, et al. Risk of ESRD and mortality in kidney and bladder stone formers. Am J Kidney Dis. 2018; published online ahead of print.

Urinary stone formation in adults increases the odds of asthma by 26%, according to a study.

Urinary stone disease (USD) in adults is associated with an increased likelihood of asthma, according to a new study.

The association is more pronounced among recurrent stone formers, individuals aged 20 to 49 years, persons with diabetes, and those who are obese.

Justin A. Lee, MD, of Albert Einstein College of Medicine in Bronx, New York, and colleagues analyzed data from 20,906 individuals aged 20 years or older who participated in the National Health and Nutrition Examination Survey (NHANES) 2007–2014, a US population-based nationally representative survey. Of these patients, 9.2% reported a history of asthma. The prevalence of asthma was significantly higher among stone-formers than non-stone formers (17.2% vs 14.4%), Dr Lee and his team reported online ahead of print in European Urology Focus.

In a fully adjusted multivariable model, stone formers had significant 26% increased odds of asthma compared with non-stone formers. Recurrent stone formers (more than 2 stones) had significant 36% increased odds. Individuals with single stones had non-significant 20% increased odds.

“These findings are exciting considering that recurrent stone formers may be a distinct group with underlying pathophysiology, whereas single stone former events may plausibly be situational rather than physiologic,” Dr Lee’s group wrote.

They explained that stone composition may differ between single stone and recurrent stone formers, “such that the higher odds for asthma in recurrent stone formers may suggest an underlying shared pathophysiology, which deserves further study.”

Among individuals aged 20 to 49 years, stone formers had significant 37% increased odds of asthma compared with non-stone formers. Among those older than 50 years, the investigators found non-significant 15% increased odds of asthma among stone formers.

In addition, the study found stronger associations between USD and asthma among diabetics and obese individuals (body mass index 30 kg/m² or higher). Among individuals with diabetes, stone formers had significant 2-fold increased odds of asthma compared with non-stone formers in a fully adjusted model; among non-diabetics, stone formers had non-significant 10% increased odds. Among obese individuals, stone formers had 41% increased odds of asthma compared with non-stone formers; among non-obese individuals, stone formers had non-significant 12% increased odds.

The authors noted that both USD and asthma have been increasing in prevalence. Metabolic syndrome (MetS) could be a factor. They pointed to a study of NHANES data (1988–1994) published in the American Journal of Kidney Diseases (2008;51:741-747) showing the prevalence of self-reported history of kidney stones among individuals aged 20 or older increased with the number of MetS traits, from 3% with none of the traits to 7.5% with 3 traits and 9.8% with 5 traits.

Insulin resistance is a characteristic of MetS, Dr Lee’s team pointed out. They cited previous studies of NHANES data linking insulin resistance with increased odds of asthma and demonstrated that worsening insulin resistance is associated with increased odds of kidney stones.

Dr Lee and his colleagues said their analysis demonstrated a significantly stronger association between urinary stones and asthma among patients with diabetes and those who were obese, “suggesting that insulin resistance may be one potential avenue of further research that could help explain the observed associations between USD and asthma.”

References

Lee JA, Abramowitz MK, Kipperman N, et al. Exploring the association of asthma with urinary stone disease: Results from the National Health and Nutrition Examination Survey 2007–2014. Eur Urol Focus. 2018; published online ahead of print.

West B, Luke A, Durazo-Avizu RA, et al. Metabolic syndrome and self-reported history of kidney stones: the National Health and Nutrition Examination Survey (NHANES III) 1988 – 1994. Am J Kidney Dis. 2008;51:741-747.