The genetic framework for development of nephrolithiasis

Over 1%-15% of the population worldwide is affected by nephrolithiasis,which remains the most common and costly disease that urologists manage today.Identification of atrisk individuals remains a theoretical and technological challenge.The search for monogenic causes of stone disease has been largely unfruitful and a technological challenge;however,several candidate genes have been implicated in the development of nephrolithiasis.In this review,we will review current data on the genetic inheritance of stone disease,as well as investigate the evolving role of genetic analysis and counseling in the management of nephrolithiasis.

Medical therapy for nephrolithiasis:State of the art

The prevalence of nephrolithiasis is increasing worldwide.Understanding and implementing medical therapies for kidney stone prevention are critical to prevent recurrences and decrease the economic burden of this condition.Dietary and pharmacologic therapies require understanding on the part of the patient and the prescribing practitioner in order to promote compliance.Insights into occupational exposures and antibiotic use may help uncover individual risk factors.Follow-up is essential to assess response to treatment and to modify treatment plans to maximize therapeutic benefit.

Effects of Nephrolithiasis on Serum DNase(Deoxyribonuclease Ⅰ and Ⅱ) Activity and E3 SUMO-Protein Ligase NSE2(NSMCE2) in Malaysian Individuals

Objective Nephrolithiasis is one of the most common disorders of the urinary tract. The aim of this study was to examine a possible relationship between DNase Ⅰ/Ⅱ activity and E3 SUMO-protein ligase NSE2 in the sera of nephrolithiasis patients to evaluate the possibility of a new biomarker for evaluating kidney damage. Methods Sixty nephrolithiasis patients and 50 control patients were enrolled in a case-control study. Their blood urea, creatinine, protein levels and DNase Ⅰ/Ⅱ activity levels were measured by spectrometry. Serum NSMCE2 levels were measured by ELISA. Blood was collected from patients of the government health clinics in Kuantan-Pahang and fulfilled the inclusion criteria. Results The result indicated that mean levels of sera NSMCE2 have a significantly increase（P〈0.01） in patients compared to control group. Compared with control subjects, activities and specific activities of serum DNase Ⅰ and Ⅱ were significantly elevated in nephrolithiasis patients（P〈0.01）. Conclusion This study suggests that an increase in serum concentrations of DNase Ⅰ/Ⅱ and E3 SUMO-protein ligase NSE2 level can be used as indicators for the diagnosis of kidney injury in patients with nephrolithiasis.

Serum E3 SUMO-protein ligase NSE2 level and peroxynitrite related to oxidative stress in nephrolithiasis patients

Objective: To prove probable relations between serum E3 SUMO-protein ligase NSE2(NSMCE2) concentration, peroxynitrite related to oxidative stress in nephrolithiasis patients.Methods: A total of 60 patients with nephrolithiasis and 50 healthy volunteers were involved in this study. Colorimetric method was used to detect blood urea, creatinine, uric acid, protein, albumin, total antioxidant status, total oxidant status, peroxynitrite, nitric oxide and oxidative stress index. Glutathione, NSMCE2 and superoxide dismutase were measured by ELISA.Results: A significant increase in level of peroxynitrite, total oxidant status, NSMCE2 and oxidative stress index in patients was observed, while total antioxidant status and glutathione were significantly decreased.Conclusions: The study concluded that serum NSMCE2 significantly correlated with peroxynitrite and oxidative stress in patients with nephrolithiasis.

The Role of Imaging in Diagnosis of Urolithiasis and Nephrolithiasis—A Literature Review Article

Urolithiasis or nephrolithiasis is a common ailment in the emergency room. The clinical presentation of a kidney stone includes fever, nausea, vomiting, acute flank pain radiating to the groin or the back. The pain is often described as stabbing and there is tachycardia, with or without hematuria for the severe patient. For the triad for urinary or kidney stones, some people say they are fever, vomiting, and acute flank pain. So in acute setting analgesia is given with or without an antiemetic to prevent vomiting IV fluids administered carefully. Noncontrast computed tomography (CT) is the gold standard for diagnosis. Most of urinary stones get washouts spontaneously if it is less than 5 mm without any intervention. However, if intervention is required either it is done by elective or as soon as possible by the intervention. I mean surgical management and surgical management will depend on how big the kidney stone is in there as well as where the kidney stone is if it is within the ureter or within the actual kidney.

Acute management of symptomatic nephrolithiasis

Over half a million patients present to emergency departments and nearly 3 million patients visit healthcare providers annually due to problems associated with urolithiasis.Despite updated guidelines from the American Urological Association and European Association of Urology for the evaluation and management of nephrolithiasis,considerable variability still exists regarding treatment for acute symptomatic upper urinary tract stones.Therefore,this article will review the current evaluation and management of acute symptomatic nephrolithiasis.Initial management includes analgesia and antiemetics.Additionally,a urinalysis and creatinine are required laboratory evaluations.Acute imaging with a non-contrast computed tomography(CT)scan is the diagnostic imaging modality of choice.However,concerns over radiation exposure have led towards low-dose and even ultra-low-dose protocols for the detection of urinary calculi.Low-dose non-contrast CT scans are now standard of care for the initial diagnosis of renal colic in patients with a body mass index≤30.Medical expulsive therapy is recommended for patients with a ureteral calculus<10 mm and no signs of infection.Emergency urinary decompression is mandatory for a specific subset of patients,especially those with infection.Although limited data exists,emergency ureteroscopy or even shock wave lithotripsy may also betherapeutic options.

Nephrectomy in a Patient with Medullary Sponge Kidney Associated with Severe Nephrocalcinosis and Nephrolithiasis: A Rare Condition

Background: Medullary sponge kidney (MSK) is a disturbance of renal development characterized by cystic dilation and diffuse precalyceal duct ectasia. The disease affects both genders in equal proportions and is generally diagnosed in adulthood, as a result of recurrent calcium nephrolithiasis and nephrocalcinosis. The most frequently encountered manifestations being renal colic, microscopic or macroscopic hematuria, and fever. The intravenous pyelogram is standard for diagnosis and metabolic workup is required to identify the underlying cause. The main goal of treatment is to prevent recurrence and disease progression. Though considered a benign condition, a nephrectomy may often be required in patients presenting late with irreversible complications and end-stage renal disease. Aim: To highlight and discuss the presentation and management of a rare case of nephrocalcinosis and nephrolithiasis secondary to the medullary sponge kidney. Case presentation: We report herein the case of a 56-year-old male with long-standing hematuria in whom a diagnosis of medullary sponge kidney disease was made and he underwent a left total nephrectomy. The postoperative course was uneventful. Conclusion: Nephrocalcinosis and nephrolithiasis are complications of MSK and can result in irreversible renal damage. A high index of suspicion is necessary for patients presenting with renal colic, recurrent urinary tract infections, or hematuria for prompt diagnosis and management.

Formulation of Ayurvedic Medicines and Extracts of Medicinal Plants as an Alternative Therapeutic Treatment Option for Nephrolithiasis

The incidence of nephrolithiasis,commonly known as kidney stone,is increasing worldwide with significant health and economic burden.Approximately 2 million people every year in India are affected by kidney stones.It affects all ages,genders,and races,but between the ages of 20 and 49 years,it affects most frequently in men than women.Different types of stones include calcium stones,cysteine stones,struvite or magnesium ammonium phosphate stones,uric acid stones,and drug-induced stones.This review article provides information about general pathophysiology,epidemiology,clinical presentation,and pharmacological treatment,which includes ayurvedic and herbal medicines for nephrolithiasis.Further understanding of the pathophysiological link between nephrolithiasis and systemic disorders is necessary for the development of new therapeutic options.

Metabolic syndrome and the urinary microbiome of patients undergoing percutaneous nephrolithotomy

Objective:To identify possible stone-promoting microbes,we compared the profiles of microbes grown from stones of patients with and without metabolic syndrome(MetS).The association between MetS and urinary stone disease is well established,but the exact pathophysiologic relationship remains unknown.Recent evidence suggests urinary tract dysbiosis may lead to increased nephrolithiasis risk.Methods:At the time of percutaneous nephrolithotomy,bladder urine and stone fragments were collected from patients with and without MetS.Both sample types were subjected to expanded quantitative urine culture(EQUC)and 16 S ribosomal RNA gene sequencing.Results:Fifty-seven patients included 12 controls(21.1%)and 45 MetS patients(78.9%).Both cohorts were similar with respect to demographics and non-MetS comorbidities.No controls had uric acid stone composition.By EQUC,bacteria were detected more frequently in MetS stones(42.2%)compared to controls(8.3%)(p=0.041).Bacteria also were more abundant in stones of MetS patients compared to controls.To validate our EQUC results,we performed 16 S ribosomal RNA gene sequencing.In 12/16(75.0%)sequence-positive stones,EQUC reliably isolated at least one species of the sequenced genera.Bacteria were detected in both“infectious”and“non-infectious”stone compositions.Conclusion:Bacteria are more common and more abundant in MetS stones than control stones.Our findings support a role for bacteria in urinary stone disease for patients with MetS regardless of stone composition.

Hypercalciuria switches Ca^(2+) signaling in proximal tubular cells,induces oxidative damage to promote calcium nephrolithiasis

Proximal tubule(PT)transports most of the renal Ca^(2+),which was usually described as paracellular(passive).We found a regulated Ca^(2+)entry pathway in PT cells via the apical transient receptor potential canonical 3(TRPC3)channel,which initiates transcellular Ca^(2+)transport.Although TRPC3 knockout(−/−)mice were mildly hypercalciuric and displayed luminal calcium phosphate(CaP)crystals at Loop of Henle(LOH),no CaP+calcium oxalate(CaOx)mixed urine crystals were spotted,which are mostly found in calcium nephrolithiasis(CaNL).Thus,we used oral calcium gluconate(CaG;2%)to raise the PT luminal[Ca^(2+)]o further in TRPC3−/−mice for developing such mixed stones to understand the mechanistic role of PT-Ca^(2+)signaling in CaNL.Expectedly,CaG-treated mice urine samples presented with numerous mixed crystals with remains of PT cells,which were pronounced in TRPC3−/−mice,indicating PT cell damage.Notably,PT cells from CaG-treated groups switched their mode of Ca^(2+)entry from receptor-operated to store-operated pathway with a sustained rise in intracellular[Ca^(2+)]([Ca^(2+)]i),indicating the stagnation in PT Ca^(2+)transport.Moreover,those PT cells from CaG-treated groups demonstrated an upregulation of calcification,inflammation,fibrotic,oxidative stress,and apoptotic genes;effects of which were more robust in TRPC3 ablated condition.Furthermore,kidneys from CaG-treated groups exhibited fibrosis,tubular injury and calcifications with significant reactive oxygen species generation in the urine,thus,indicating in vivo CaNL.Taken together,excess PT luminal Ca^(2+)due to escalation of hypercalciuria in TRPC3 ablated mice induced surplus CaP crystal formation and caused stagnation of PT[Ca^(2+)]i,invoking PT cell injury,hence mixed stone formation.

Protective effects of Cuminum cyminum L.essential oil on ethylene glycol induced nephrolithiasis in mice

Objective:To investigate the protective effect of Cuminum cyminum(C.cyminum)essential oil on ethylene glycol induced nephrolithiasis in mice.Methods:The study comprised of the following four different groups of six mice:ethylene glycol group,C.cyminum group,treatment group and normal group.The levels of blood urea nitrogen and creatinine were analyzed and the kidney samples from all the animals of each group were stained with haematoxylin and eosin.Results:Treatment group revealed mild tubular degeneration without formation of calcium oxalate crystals and protein deposition.There were no significant differences between serum levels of blood urea nitrogen and creatinine in treatment and normal groups.Conclusions:It seems that C.cyminum essential oil significantly decreased formation of calcium oxalate crystals and the growth of renal calculi in different parts of the tubules.

Present indications and techniques of percutaneous nephrolithotomy:What the future holds?

The purpose of the review was to present the latest updates on percutaneous nephrolithotomy(PCNL)procedure in terms of indications and evolving techniques,and to identify the advantages and disadvantages of each modality.The data for this review were collected after a thorough PubMed search in core clinical journals in English language.The key words included“PCNL”and“PNL”in combination with“indications”,“techniques”,“review”and“miniaturized PCNL”.Publications relevant to the subject were retrieved and critically reviewed.Current European and American Urology Association Nephrolithiasis Guidelines were included as well.The indications for standard PCNL have been changed through the past decade.Despite evolution of the procedure,innovations and the development of new technical approaches,the indications for miniaturized PCNL have not been standardized yet.There is a need for well-constructed randomized trials to explore the indications,complications and results for each evolving approach.A continuous reduction of tract size is not the only revolution of the last years.There is constant ongoing interest in developing new efficient miniature instruments,intracorporeal lithotripters and sophisticated tract creation methods.We can summarize that,PCNL represents a valuable well-known tool in the field of endourology.We should be open minded to future changes in surgical approaches and technological improvements.

Indications and contraindications for shock wave lithotripsy and how to improve outcomes

For over 35 years shock wave lithotripsy has proven to be an effective,safe and truly minimally invasive option for the treatment of nephrolithiasis.Various technical factors as well as patient selection can impact the success of the procedure.We used published work focusing on outcomes of shock wave lithotripsy,risk of complications,and strategies for improving stone fragmentation to create this review.Multiple patient and technical factors have been found to impact success of treatment.Skin to stone distance,stone density and composition,size and location of the stone within the urinary system all influence stone free rates.A slower rate with a gradual increasing voltage,precise targeting,proper coupling will improve stone fragmentation and decrease risk of complications.The selection of appropriate patients through a shared decision making process and attention to the technical factors that improve stone free rates is key to providing an effective treatment and patient satisfaction.

Characterization of ureteral stents by dual-energy computed tomography: Clinical implications

Dual-energy computed-tomography(DECT) has been suggested as the method of choice for imaging urinary calculi due to the modality's high sensitivity for detect-ing stones and its capability of accurately differentiat-ing between uric-acid(UA) and non-UA(predominantly calcium) stones. The clinical significance of the latter feature relates to the differences in management of UA vs non-UA calculi. Like calculi, ureteral stents are assigned color by the dual-energy post-processing algorithm, which may lead to improved or worsened stone visualization based on the resulting stent/stone contrast. Herein we depict the case of a nephrolithiasis patient with bilateral stents, each with different color, clearly displaying the effect of stent color on stone vi-sualization. Further, three-dimensional reconstruction of the DECT images illustrates advantages of this enhancement compared to conventional two-dimensional computed tomography. The resulting stent/stone contrast produces an unanticipated potential advantage of DECT in patients with urolithiasis and stents and may promote improved management decision-making.

Incidence of kidney stones in kidney transplant recipients:A systematic review and meta-analysis

AIM To evaluate the incidence and characteristics of kidney stones in kidney transplant recipients. METHODS A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from the inception of the databases through March 2016. Studies assessing the incidence of kidney stones in kidney transplant recipients were included. We applied a randomeffects model to estimate the incidence of kidney stones.RESULTS Twenty one studies with 64416 kidney transplant patients were included in the analyses to assess the incidence of kidney stones after kidney transplantation. The estimated incidence of kidney stones was 1.0%(95%CI: 0.6%-1.4%). The mean duration to diagnosis of kidney stones after kidney transplantation was 28 ± 22 mo. The mean age of patients with kidney stones was 42 ± 7 years. Within reported studies, approximately 50% of kidney transplant recipients with kidney stones were males. 67% of kidney stones were calcium-based stones(30% mixed CaO x/CaP, 27%CaO x and 10%CaP), followed by struvite stones(20%) and uric acid stones(13%).CONCLUSION The estimated incidence of kidney stones in patients after kidney transplantation is 1.0%. Although calcium based stones are the most common kidney stones aftertransplantation, struvite stones(also known as "infection stones") are not uncommon in kidney transplant recipients. These findings may impact the prevention and clinical management of kidney stones after kidney transplantation.

Morphometry scores: Clinical implications in the management of staghorn calculi

Due to their large size,rapid growth,and attendant morbidity,staghorn calculi are complex clinical entities that impose significant treatment-related challenges.Moreover,their relative heterogeneitydin terms of both total stone burden and anatomic distributiondlimits the ability to standardize their characterization and the reporting of surgical outcomes.Several morphometry systems currently exist to define the volumetric distribution of renal stones,in general,and to predict the outcomes of percutaneous nephrolithotomy;however,they fall short in their applicability to staghorn stones.In this review,we aim to discuss the clinical utility of morphometry systems and the influence of pelvicalyceal anatomy on the management of these complex calculi.

Serratia fonticola and its role as a single pathogen causing emphysematous pyelonephritis in a non-diabetic patient:A case report

BACKGROUND Diagnosis of emphysematous pyelonephritis has been described around the world for some decades,frequently associated with Escherichia coli and other anaerobic,gas-forming bacteria and mostly in patients living with diabetes.We present a case report of emphysematous pyelonephritis in a non-diabetic patient caused by Serratia fonticola as well as a brief literature review to draw attention to this rare pathogen as a cause of pyelonephritis.CASE SUMMARY A 38-year-old female presented with fever,severe pain in the right flank and changes in urinary habits.She was admitted,and emphysematous pyelonephritis was confirmed by an abdominal computerized tomography and urine cultures;the latter showed Serratia fonticola as a single pathogen.After 3 d of being treated with piperacillin/tazobactam and percutaneous drainage she became afebrile,and the gas presence reduced.CONCLUSION Emphysematous pyelonephritis infections in non-diabetic patients are rare but can be severe and life-threatening.This case suggests that Serratia fonticola infection can occur in patients undergoing invasive or instrumented procedures.

Advances in percutaneous stone surgery

Treatment of large renal stones has changed considerably in recent years.The increasing prevalence of nephrolithiasis has mandated that urologists perform more surgeries for large renal calculi than before,and this has been met with improvements in percutaneous stone surgery.In this review paper,we examine recent developments in percutaneous stone surgery,including advances in diagnosis and preoperative planning,renal access,patient position,tract dilation,nephroscopes,lithotripsy,exit strategies,and post-operative antibiotic prophylaxis.

Fatal Urosepsis: A 41 Year-Old Pregnant Woman—Case Report

Introduction: Urinary tract infections are one of the most frequent infectious complications during pregnancy [1], while acute pyelonephritis is the main non-obstetric reason for hospitalisation [2] [3]and septic shock in pregnant women. Objectives and methods: The aim of our study is to analyse the diagnostics and treatment of a 41-year-old pregnant woman with the most severe form of urinary tract infection—urosepsis. Case report: A 41-year old woman in the 12th week of pregnancy hospitalised at Intensive Care Unit (ICU) after urological intervention (JJ stent). On the first day after the intervention, the patient was diagnosed as having urosepsis. Scores: SOFA 14 pts, APACHE II 26 pts, SAPS II SCORE 61 pts. Second day in ICU: spontaneous abortion. Microbiological?investigation: Escherichia coli—extended-spectrum beta-lactamase (ESBL+). Conclusions: Apregnant patient with a complicated infection of the urinary system ought to be treated in a multi-profile hospital, offering a possibility to consult doctors of various specialisations (urologist, gynaecologist, anaesthesiologist, nephrologist) as well as full access to a radiology laboratory, which will ensure the choice of appropriate and safe treatment for both the mother and the developing foetus.

Clinical research on curative effect of treatment on patients with gouty renal stone by hydration-alkalization therapy

Objective:Study the clinical effect of intravenous hydration and alkalization therapy on uric acid nephrolithiasis.Methods: Sixty-five patients with 86 stones admitted to Department of Endocrinology and Urinary Nephropathy from December 2015 to December 2017 in our hospital were divided into control group (n= 31) and Treatment group (n = 34) with at random. Both groups were given basic treatment with low purine diet and the control group was treated with oral sodium bicarbonate tablets + oral rehydration 1000 mL / d. The treatment group was treated with hydration alkalosis treatment by 0.9% saline 500 mL + 5% sodium bicarbonate injection of 60 mL + 10% potassium chloride injection 10 mL intravenous infusion, 2 times/d. Two groups were treated for a course of treatment (10 d), respectively, detecting relevant laboratory parameters and imaging studies before and after treatment for assessing the effectiveness of treatment.Result: The total effective rate of the treatment group was 86.67%, which was significantly better than the control group (4.88%).Conclusion: It is a significant effect that Intravenous hydration alkalosis therapy for the treatment of uric acid nephrolithiasis. The diameter of less than 0.5 cm stones disappears, and the diameter of 0.5-0.8 cm stone was significantly reduced. As it can improve stone related renal insufficiency with low cost, it is widely recommended in clinical.