Roswitha Siener

Objectives: This study compared the risk profiles, nutrient intake, and kidney function of calcium oxalate stone formers with and without enteric hyperoxaluria. Methods: Thirty-seven patients with calcium oxalate stone disease and enteric hyperoxaluria (cases) and 37 sex- and age-matched idiopathic calcium oxalate stone formers (controls) were enrolled. Patients did not receive any nutritional counseling prior to the start of the study, and they discontinued medications affecting urinary parameters four weeks before their study participation. Anthropometric, clinical, and metabolic parameters were recorded. Dietary and 24-h urinary variables were measured under the habitual diet and under a balanced, standardized diet. The [¹³C₂] oxalate absorption and calcium loading tests were carried out. Results: The median [¹³C₂] oxalate absorption was significantly higher in cases (14.8%) than in controls (8.9%). Under the balanced diet, hypocitraturia, hypomagnesuria, low urine volume and pH value were significantly more common in the case group, whereas hypercalciuria occurred more frequently in the control group, affecting 45.9% of controls and 5.4% of cases. Furthermore, the control group exhibited a greater reduction in urinary calcium excretion under the balanced diet. Urinary oxalate excretion and the ion-activity product index of calcium oxalate were significantly higher under both diets, with a greater decline observed in the case group under the balanced diet. The estimated glomerular filtration rate (eGFR) was lower in cases. A multivariable linear regression analysis revealed a significant association between urine pH and eGFR. Conclusions: Calcium oxalate stone formers with and without enteric hyperoxaluria benefit from a balanced diet and sufficient fluid intake. The reduction in urinary oxalate excretion and the biochemical risk of recurrent calcium oxalate stone formation were even more pronounced in patients with enteric hyperoxaluria. Particular attention should be paid to low urine pH, as it is hypothesized to be a potential indicator of impaired kidney function.

Purpose: This umbrella review aimed to investigate the evidence for an association of dietary intake of total protein as well as animal and plant protein with the incidence of coronary heart disease (CHD), stroke and total cardiovascular diseases (CVD). Methods: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis (MA) published between January 2012 and April 2024. Methodological quality, outcome-specific certainty of evidence, and overall certainty of evidence were assessed using established tools and predefined criteria. Results: Ten SRs were considered eligible for the umbrella review; all were based on prospective cohort studies, and six conducted a MA. Dietary intakes of total, animal and plant protein were not associated with the risk of CHD or stroke. For CHD, the overall certainty of evidence for the absence of an association was “probable” for total, animal and plant protein. For stroke and total CVD, the overall certainty of evidence was rated as “possible” for the absence of an association with the intake of total protein and plant protein and insufficient for animal protein intake. Conclusion: Given that most SRs on dietary protein intake did not indicate an association, it seems that protein intake plays no major role in the development of CVD. This investigation was registered at PROSPERO as CRD42018082395.

The formation of kidney stones is a complex biologic process involving interactions among genetic, anatomic, dietary, and environmental factors. Traditional lithogenic models were based on urine supersaturation in relation to the activity of crystallization promoters and inhibitors. However, modern research has added new principles such as the “renal epithelial cell response” and the role of inflammation and oxidative stress leading to the development of a “multi-hit hypothesis”. A strong correlation between urinary stones and kidney damage has been well demonstrated by both cohort and case-control studies. The main contributors to chronic kidney damage associated with urinary stones include crystal deposition within the renal parenchyma, associated comorbidities, repeated obstructive and infectious episodes, as well as the potential adverse effects of stone removal procedures. Most hereditary stones may cause high urinary saturation levels promoting obstruction of the Bellini ducts and consequent glomerulosclerosis and interstitial fibrosis in the cortex. These include hereditary hypercalciurias, primary hyperoxalurias, cystinuria, adenine phosphoribosyltransferase (APRT) deficiency (associated with 2,8-dihydroxyadenine lithiasis) and xanthinuria. Complete distal renal tubular acidosis occurs in childhood and presents deafness, rickets, and a short life expectancy. The incomplete form usually manifests in adulthood, primarily with recurrent urinary lithiasis, and less frequently with nephrocalcinosis. In all stone formers stone analysis and a basic metabolic evaluation, including blood biochemistry, urine sediment examination, urinary pH and culture are mandatory, in contrast high-risk stone formers require a more specific metabolic evaluation, including a 24-hour urine sample to measure calcium, phosphate, citrate, oxalate, uric acid, magnesium, sodium and proteinuria. The morpho compositional analysis of kidney stones offers essential insights beyond merely identifying their predominant chemical component. This approach reveals key aspets of the stone formation, such as nucleation sites, crystal growth patterns, and the presence of specific lithogenic processes. The ideal analytical protocol combines stereoscopic microscopy (StM), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and, when necessary, Fourier-transform infrared spectroscopy (FTIR). Recurrence prevention and managing residual fragments require complementary strategies such as lifestyle modifications, dietary interventions, and pharmacological therapies. Among pharmacological options, alkaline citrate salts, particularly potassium citrate, are widely used due to their ability to modify urinary chemistry and inhibit stone formation. Recently, novel molecules have been introduced into the management of renal stone disease. Phytate a naturally occurring polyphosphorylated carbohydrate, exibits a potent inhibitory effect on calcium salt’s nucleation, growth, and aggregation. Theobromine, another natural compound, has been shown to effectively inhibit uric acid crystallization. The co-administration of urinary alkalinizing agents, such as potassium citrate, alongside theobromine has been proposed as a therapeutic strategy to optimize uric acid solubility and to reduce the risk of excessive alkalinization and subsequent sodium urate precipitation. Struvite stones are caused by urinary tract infection with urease- producing microorganisms. Their treatment requires specific measures including complete surgical stone removal, short or long-term antibiotic treatment, to maintain urinary acidification to a pH below 6.2, and a urine volume of at least 2 litres/24 hours. L-methionine has been shown to effectively lower urine pH and the relative supersaturation of struvite. An essential aspect of medical management of urinary stone disease is treatment adherence, which depends on perceived benefit, treatment duration, and side effect profile. The side effects of citrate treatment are mild gastrointestinal disorders whereas thiazide diuretics tend to cause hypokalemia-related symptoms and less frequent metabolic and dermatologic side effects. Urease inhibitors for struvite stones and drugs used to enhance cystine solubility are more frequently associated with side effects. The use of smartphone applications can support patients by promoting adequate hydration, adherence to dietary recommendations, and compliance with prophylactic medication. Endoscopic techniques currently play a prevalent role in the removal of renal stones, while extracorporeal shock wave lithotripsy is today marginally used for specific indications. Different technical modalities can be used for percutaneous nephrolithotomy (PCNL), each with its own advantages and disadvntages (standard vs. mini, prone vs. supine, fluoroscopic vs ultrasound-guided). Flexible ureteroscopy or retrograde intrarenal renal surgery (RIRS) has extended its indications due to technological advancements in endoscopes and their accessories. The availability of new laser technologies (thulium fiber laser and pulse-modulated Ho:YAG laser) has enhanced stone fragmentation and dusting capabilities. However, their use exposes the renal parenchyma to high temperatures and pressures which could potentially contribute to renal damage. Factors influencing heat release include laser type and settings, exposure time, stone location, fiber-to-stone distance, irrigation volume and fluid circulation. Reduction of heat release can be achieved by limiting the laser settings to reasonable values or by improving fluid circulation with use of ureteral access sheaths, especially those navigable and equipped with suction. High intrarenal pressure is also closely associated with renal damage. Sustained high pressure or even pressure spikes may increase this risk, highlighting the importance of real-time pressure monitoring through sensors...

This study investigated the risk profile and the impact of dietary intervention in calcium oxalate stone formers with enteric hyperoxaluria under controlled, standardized conditions. Thirty-seven patients were included in the study. Dietary and 24-h urinary parameters were obtained on the self-selected diet and a balanced, standardized diet. Tests for [¹³C₂]oxalate absorption, calcium- and ammonium chloride-loading were performed. Mean [¹³C₂]oxalate absorption was 18.8%. A significant positive association was observed between urinary oxalate excretion and intestinal oxalate absorption. In addition, urinary oxalate excretion was significantly correlated with dietary oxalate intake. Mean urinary oxalate excretion decreased from 0.841 mmol/24 h on the usual diet to 0.662 mmol/24 h on the balanced diet, corresponding to a reduction of 21.3%. Besides hyperoxaluria, hypocitraturia and hypomagnesuria were the most common urinary abnormalities at baseline, being present in 83.8% and 81.1% of patients, respectively. Urinary citrate increased by 50.9% and magnesium excretion increased by 25.2% on the balanced diet. As a result, the relative supersaturation of calcium oxalate declined significantly (by 36.2%) on the balanced diet. Since 41% of patients on the balanced diet still had a urine volume of less than 2.0 L/24 h, efforts should be made to increase urine volume by increasing fluid intake and reducing intestinal fluid losses. Dietary intervention proved to be effective in reducing urinary oxalate excretion and should be a cornerstone of the treatment of patients with enteric hyperoxaluria.

Zusammenfassung Die Urolithiasis ist eine der häufigsten urologischen Erkrankungen. Die Abklärung der Ursachen der Steinbildung bildet die Grundlage für eine erfolgreiche Rezidivprävention. Die metabolische Diagnostik und die rezidivpräventiven Maßnahmen richten sich nach der Zuordnung des Harnsteinpatienten zur Niedrig- oder Hochrisikogruppe. Die Harnsteinanalyse ist eine essenzielle Voraussetzung für die Identifikation von Risikopatienten. Die allgemeinen Empfehlungen zu Ernährung und Lebensstil gelten als Basistherapie. In Abhängigkeit von der Steinart und dem individuellen biochemischen Risikoprofil eines Patienten sollten diese allgemeinen Maßnahmen durch eine gezielte ernährungsmedizinische und pharmakologische Therapie ergänzt werden. Mischsteine können eine Herausforderung für die Therapie und Rezidivprävention darstellen. Eine personalisierte Therapieentscheidung, die die verschiedenen Komponenten von Mischsteinen berücksichtigt, könnte die Rezidivprävention der Urolithiasis weiter verbessern.

Introduction: This umbrella review aimed to investigate the evidence of an effect of dietary intake of total protein, animal and plant protein on blood pressure (BP), and hypertension (PROSPERO: CRD42018082395). Methods: PubMed, Embase and Cochrane Database were systematically searched for systematic reviews (SRs) of prospective studies with or without meta-analysis published between 05/2007 and 10/2022. The methodological quality and outcome-specific certainty of evidence were assessed by the AMSTAR 2 and NutriGrade tools, followed by an assessment of the overall certainty of evidence. SRs investigating specific protein sources are described in this review, but not included in the assessment of the overall certainty of evidence. Results: Sixteen SRs were considered eligible for the umbrella review. Ten of the SRs investigated total protein intake, six animal protein, six plant protein and four animal vs. plant protein. The majority of the SRs reported no associations or effects of total, animal and plant protein on BP (all “possible” evidence), whereby the uncertainty regarding the effects on BP was particularly high for plant protein. Two SRs addressing milk-derived protein showed a reduction in BP; in contrast, SRs investigating soy protein found no effect on BP. The outcome-specific certainty of evidence of the SRs was mostly rated as low. Discussion/conclusion: This umbrella review showed uncertainties whether there are any effects on BP from the intake of total protein, or animal or plant proteins, specifically. Based on data from two SRs with milk protein, it cannot be excluded that certain types of protein could favourably influence BP.

Nephrolithiasis is a common urologic manifestation of Crohn’s disease. The purpose of this study was to investigate the clinical characteristics, intestinal oxalate absorption, and risk factors for urinary stone formation in these patients. In total, 27 patients with Crohn’s disease and 27 healthy subjects were included in the present study. Anthropometric, clinical, and 24 h urinary parameters were determined, and the [¹³C₂]oxalate absorption test was performed. Among all patients, 18 had undergone ileal resection, 9 of whom had a history of urinary stones. Compared to healthy controls, the urinary excretion values of calcium, magnesium, potassium, sulfate, creatinine, and citrate were significantly lower in patients with Crohn’s disease. Intestinal oxalate absorption, the fractional and 24 h urinary oxalate excretion, and the risk of calcium oxalate stone formation were significantly higher in patients with urolithiasis than in patients without urolithiasis or in healthy controls. Regardless of the group, between 83% and 96% of the [¹³C₂]oxalate was detected in the urine within the first 12 h after ingestion. The length of ileum resection correlated significantly with the intestinal absorption and urinary excretion of oxalate. These findings suggest that enteric hyperoxaluria can be attributed to the hyperabsorption of oxalate following extensive ileal resection. Oral supplementation of calcium and magnesium, as well as alkali citrate therapy, should be considered as treatment options for urolithiasis.

Proper analysis of urinary stone composition is a cornerstone for diagnosis, targeted treatment and recurrence prevention of urolithiasis. The aim of this study was to determine the composition, frequency and distribution of mixed stones according to gender and age of patients. A total of 42,519 urinary stones from 30,311 men and 12,208 women submitted between January 2007 and December 2020 were studied. Most urinary calculi consisted of two components (50.9%), followed by stones of a single constituent (27.1%) and three-component stones (21.9%), while four-component stones were only rarely identified (0.1%). Among all stones, 49.8% consisted of whewellite (COM), weddellite (COD), and mixtures of COM and COD, 33.8% were pure carbonate apatite (CA) and mixtures of CA with COM and/or COD, while 7.6% were composed of uric acid anhydrous (UAA), uric acid dihydrate (UAD), and mixed UAA and UAD. The remaining 8.8% of calculi were rare single-component stones and rare mixtures of various constituents. The number of stone components was inversely associated with age (p < 0.001). The proportion of men decreased significantly with the number of stone constituents, from 3.01:1 for single-component stones to 1.0:1 for four-component urinary calculi (p < 0.001). The vast majority of urinary calculi consisted of two or more components in varying proportions. While age was inversely associated with the number of stone constituents, the proportion of women increased significantly from single-component to four-component urinary calculi. A significant proportion of mixed stones could present a challenge for diagnosis and targeted recurrence prevention.

Purpose: This umbrella review aimed to assess whether dietary protein intake with regard to quantitative (higher vs. lower dietary protein intake) and qualitative considerations (total, plant-based or animal-based protein intake) affects body weight (BW), fat mass (FM) and waist circumference (WC). Methods: A systematic literature search was conducted in PubMed, Embase and Cochrane Database of Systematic Reviews for systematic reviews (SRs) with and without meta-analyses of prospective studies published between 04 October 2007 and 04 January 2022. Methodological quality and outcome-specific certainty of evidence of the retrieved SRs were assessed by using AMSTAR 2 and NutriGrade, respectively, in order to rate the overall certainty of evidence using predefined criteria. Results: Thirty-three SRs were included in this umbrella review; 29 were based on randomised controlled trials, a few included cohort studies. In studies without energy restriction, a high-protein diet did not modulate BW, FM and WC in adults in general (all “possible” evidence); for older adults, overall certainty of evidence was “insufficient” for all parameters. Under hypoenergetic diets, a high-protein diet mostly decreased BW and FM, but evidence was “insufficient” due to low methodological quality. Evidence regarding an influence of the protein type on BW, FM and WC was “insufficient”. Conclusion: “Possible” evidence exists that the amount of protein does not affect BW, FM and WC in adults under isoenergetic conditions. Its impact on the reduction in BW and FM under hypoenergetic conditions remains unclear; evidence for an influence of protein type on BW, FM and WC is “insufficient”.

This study examined the profile of patients and the impact of diet on the risk of brushite stone formation under controlled, standardized conditions. Sixty-five patients with brushite nephrolithiasis were enrolled in the study. Metabolic, dietary, and 24 h urinary parameters were collected under the habitual, self-selected diet of the patients and the balanced mixed, standardized diet. The [¹³C₂]oxalate absorption, ammonium chloride, and calcium loading tests were conducted. All patients had at least one abnormality on the usual diet, with hypercalciuria (84.6%), increased urine pH (61.5%), and hyperphosphaturia (43.1%) being the most common. Absorptive hypercalciuria was present in 32.1% and hyperabsorption of oxalate in 41.2%, while distal renal tubular acidosis (dRTA) was noted in 50% of brushite stone formers. The relative supersaturation of brushite did not differ between patients with and without dRTA. Among all recent brushite-containing calculi, 61.5% were mixed with calcium oxalate and/or carbonate apatite. The relative supersaturation of brushite, apatite, and calcium oxalate decreased significantly under the balanced diet, mainly due to the significant decline in urinary calcium, phosphate, and oxalate excretion. Dietary intervention was shown to be effective and should be an integral part of the treatment of brushite stone disease. Further research on the role of dRTA in brushite stone formation is needed.