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.

Role of insulin resistance in uric acid nephrolithiasis

Metabolic syndrome has been implicated in the pathogenesis of uric acid stones.Although not completely understood,its role is supported by many studies demonstrating increased prevalence of uric acid stones in patients with metabolic syndrome and in particular insulin resistance,a major component of metabolic syndrome.This review presents epidemiologic studies demonstrating the association between metabolic syndrome and nephrolithiasis in general as well as the relationship between insulin resistance and uric acid stone formation,in particular.We also review studies that explore the pathophysiologic relationship between insulin resistance and uric acid nephrolithiasis.

Confounding risk factors and preventative measures driving nephrolithiasis global makeup

Nephrolithiasis is increasing in developed and developing countries at an alarming rate. With the global spike in kidney stone diseases, it is crucial to determine what risk factors are influencing the current global landscape for kidney stones. Our aims for this review are: to identity and analyze the four categories of risk factors in contributing to the global scale of stone formation: lifestyle, genetics, diet, and environment; and discuss preventative measures for kidney stone formation. We also performed data search through the published scientific literature, i.e., PubMed~? and found that there is a significant link between lifestyle and obesity with cases of calcium stones. Food and Agriculture Organization of the United Nations and World Health Organization factor indicators for dietary intake and obesity, along with climate data were used to create the projected total risk world map model for nephrolithiasis risk. Complete global analyses of nephrolithiasis deplete of generalizations is nearly insurmountable due to limited sources of medical and demographic information, but we hope this review can provide further elucidation into confounding risk factors and preventative measures for global nephrolithiasis analysis.

From crystalluria to kidney stones,some physicochemical aspects of calcium nephrolithiasis

Nephrolithiasis seems to be the result of crystal formation,aggregation and retention in the kidney during crystalluria.These processes have to occur within the short urinary transit time through the kidney being in the order of few minutes.Recently much work was done on rather qualitative aspects of nephrolithiasis like genetics,metabolism and morphology.In this review we try to provide some quantitative information on urinary supersaturation with respect to stone minerals,especially Ca oxalate(CaO x),on the formation and aggregation of Ca Ox crystals and on crystal retention in the kidney.The paper is centered on idiopathic Ca nephrolithiasis being the most frequent stone disease with only partially known pathogenesis.New aspects of the role of urinary macromolecules in stone formation and of the mechanism of crystal aggregation are provided.

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.

Preventive and therapeutic effects of Aerva lanata(L.) extract on ethylene glycol-induced nephrolithiasis in male Wistar albino rats

Objective Nephrolithiasis is a common urological disease. This study aims to evaluate the preventive and therapeutic effects of hydro-alcoholic extract of Aerva lanata(L.) roots(HAEAL) on ethylene glycol-induced nephrolithiasis in rats.Methods Fifty grams of shade-dried coarsely powdered Aerva lanata(L.) root was successively extracted with organic solvents in increasing order of polarity [petroleum ether(60-80 ℃), chloroform, and ethanol] using a Soxhlet apparatus, and then concentrated. Physical tests including nature, color, odor, and texture were performed on the herbal suspension. In vitro nephrolithiasis assessment was performed by nucleation assay, aggregation assay, and crystal growth assay. Thirty adult male Wistar albino rats were randomly divided into five groups(six rats in each group). Group 1: negative control group without induction or treatment till day 28. Group 2: positive control group receiving a daily oral solution of 0.75% ethylene glycol till day 14, and mixed with distilled water till day 28. Group 3: standard group receiving a daily oral solution of 0.75% ethylene glycol till day 14 and Cystone(750 mg/kg) from day 15 to day 28. Group 4: low dose HAEAL group receiving a daily oral solution of 0.75%ethylene glycol till day 14, and 400 mg/kg HAEAL from day 15 to day 28(1 mL per day). Group 5: high dose HAEAL group receiving a daily oral solution of 0.75% ethylene glycol till day 14,and 800 mg/kg HAEAL from day 15 to day 28(1 mL per day). Urine(urine volume, pH value,appearance, odor, and turbidity) examination and serum test were performed. On day 29, the kidneys were dissected, and histopathology examination was performed to determine the degree of tubular injury.Results The suspension showed stability and aroma with no turbidity at room temperature.The suspension did not show changes in color and odor until day 3, indicating that the preparation was stable for 72 h. Body weight decreased in the positive control group indicating stone formation and changes in water intake. Both standard and HAEAL treatments restored the body weight to normal levels after treatment, indicating the beneficial effects of the treatment. Histopathological examination revealed no significant findings in the negative control group, whereas the positive control group showed inflammation in the kidney parenchyma.Compared with positive control group, there was increase in urine volume and excretion of urinary constituents such as calcium and oxalate(P < 0.01) as well as improved clearance rate(P < 0.05) in HAEAL treatment groups, in addition, the urine pH value of HAEAL groups was increased.Conclusion HAEAL reduced nephrolithiasis formation and had a diuretic effect, which could be used to promote the expulsion of stones. Further studies are needed to enhance the stability of the suspension for the production of better pharmaceutical formulations.

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.

Bilateral nephrolithiasis and upper tract transitional cell carcinoma in horseshoe kidney

Nephroureterectomy is currently the criterion-standard treatment for high-grade upper tract urothelial carcinoma(UTUC).Current guidelines and expert opinions propose some exceptions to this approach based on patient characteristics,disease status,and function of the contralateral kidney.We present a rare case of a patient with horseshoe kidney,bilateral large nephrolithiasis,high-grade UTUC in one moiety,and relative parenchymal thinning of the contralateral side.The patient was treated with a percutaneous,minimally invasive,nephron sparing approach.The patient also had intracollecting system instillations of gemcitabine and docetaxel.Minimally invasive percutaneous resection of high-grade UTUC is a safe procedure in select cases.Current guidelines may not apply to all patients;unique scenarios with UTUC may require personalized decision-making and treatment at specialized centers.

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.

Factors and Cut-Off Predicting Stone Passage under Medical Expulsive Therapy (MET)

Background: Ureteral stones are the most common leading cause of acute flank pain. This study aimed to identify sociodemographic and clinical variables predicting spontaneous ureteral stone passage and determine the optimal size cut-off for predicting such passage. Method: We conducted a retrospective evaluation of patients presenting with acute renal colic at a urology outpatient clinic. Patients with ureteral stones ≤ 10 mm and no surgical intervention post-initial diagnosis, who attended follow-up visits, were included. Exclusion criteria comprised stone size > 1 cm, fever due to obstructive pyelonephritis, acute kidney injury, single kidney status, or bilateral ureteral obstruction. Results: Of 124 included patients, the spontaneous stone passage rate was 57.3%, with a mean passage time of 11.1 (SD 6.25) days. Bivariate analysis revealed that factors predicting spontaneous passage were stone size (p Conclusions: Stone size < 7 mm, UVJ or distal ureter location, emerged as key predictors of stone passage in nephrolithiasis, and stone size below 6.85 mm is a reasonable cut off to initiate MET rather than 10 mm.

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.

Nephropathy in dietary hyperoxaluria:A potentially preventable acute or chronic kidney disease

Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis,but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma,profound tubular damage and interstitial inflammation and fibrosis.Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to endstage renal disease(ESRD).This sequence of events,well recognized in the past in primary and enteric hyperoxalurias,has also been documented in a few cases of dietary hyperoxaluria.Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide,thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions.Studies addressing this question have the potential of improving population health and should be undertaken,alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate,and into the mechanisms of development of oxalate-induced renal parenchymal disease.Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies.