Avoiding "Needless" nephrectomy: What is the role of small renal mass biopsy in 2024?

Current guidelines do not mandate routine preoperative renal mass biopsy (RMB) for small renal masses (SRMs), which results in a considerable rate (18%-26%) of needless nephrectomy/partial nephrectomy for benign renal tumors. In light of this ongoing practice, a narrative review was conducted to examine the role of routine RMB for SRM. First, arguments justifying the current non-biopsy approach to SRM are critically reviewed and contested. Second, as a standalone procedure, RMB is critically assessed; RMB was found to have higher sensitivity, specificity, and an equal or lower complication rate when compared with other commonly preoperatively biopsied solid organ tumors (e.g., breast, prostate, lung, pancreas, thyroid, and liver). Based on the foregoing information, we propose a paradigm shift in SRM management, advocating for an updated policy in which partial nephrectomy or nephrectomy for SRM invariably occurs only after a preoperative biopsy confirms that a SRM is indeed malignant.

Comparison of Ureteral Stent Biomaterials: Encrustation Profile in Lithogenic Artificial Urine Models.

Ureteral stent encrustation significantly limits indwelling time and can lead to downstream urological problems. However, no ideal polymeric biomaterials have been shown to completely resist encrustation in long-term urine exposure. Recently, 2-hydroxyethyl methacrylate (HEMA)-coated Pellethane was reported as a promising biomaterial resistant to encrustation. This study compared HEMA-coated Pellethane to commercially available stents under two different artificial urine environments. To evaluate the degree and composition of encrustation on HEMA-coated Pellethane, Boston Scientific Tria, Bard InLay Optima, Cook Universa Hydrogel, and Cook Black Silicone stents were used at various dwelling times in two different artificial urine environments. In a batch-flow model, samples of stents were suspended in an artificial urine solution (AUS) at 37 °C. Every 24 h for 11 weeks, 50% of the AUS would be replaced with fresh components using a programmable peristaltic pump system. The stent materials were removed at suitable time intervals and air-dried for 24 h under sterile conditions before follow-up analysis. SEM was used to assess the degree of encrustation, and inductively coupled plasma mass spectrometry (ICP-MS) was employed to quantify the encrusted compositions, specifically for calcium, magnesium, and phosphorus. We measured the weight gain over time due to encrusted deposits on the stents and quantified the amount of Ca, Mg, and P deposited on each encrusted stent. After the 11 week trial, HEMA-coated Pellethane showed the most average mass change. SEM showed that HEMA-coated Pellethane was fully encrusted in just 2 weeks in the AUS environments, and ICP-MS showed that Ca is the most abundant deposit. Among all the tested stents, Black Silicone performed the best. The two AUSs were formulated to encrust more rapidly than physiological conditions. HEMA-coated Pellethane is not an ideal stent material, while silicone is a promising material for advancing ureteral stents.

Evaluation of Renal Function and Stent Durability Following Resonance Stent Placement for Benign Disease.

Introduction: The metal-based Resonance stent (RS) has traditionally been placed in patients with malignant ureteral obstruction; as such, the long-term utility of RS among patients with benign ureteral obstruction (BUO) remains underinvestigated. Methods: We retrospectively reviewed our database for patients with BUO who underwent RS placement between 2010 and 2020. The impact of chronic RS placement on renal function was evaluated by estimated serum creatinine-based glomerular filtration rate (eGFR), furosemide renal scan, and CT-based renal parenchymal volume measurement. The number of and reason for RS stent exchanges during the follow-up period, incidence of encrustation, and the average indwell time were recorded. A cost analysis of placing the RS vs a polymeric stent was performed. Results: Among 43 RS patients with BUO, at a mean follow-up of 26 months, there was no change in eGFR (p = 0.99), parenchymal volume (p = 0.44), or split renal function of the stent-bearing side on renal scan (p = 0.48). The mean RS indwell time was 9.7 months. Eleven patients (26%) underwent premature stent replacement (6 cases) or removal (5 cases). Stents in 9 patients (32%) were encrusted, of which 4 (44%) required laser lithotripsy. Overall, 25 patients (58%) and 12 patients (28%) had a mean stent indwell time of ≥6 months and ≥12 months, respectively. Placing an RS resulted in a 52%, 37%, and 5.6% cost reduction compared with a regular polymeric stent placement, where it was exchanged every 6, 4, or 3 months, respectively. Conclusions: RS deployment in the patient with a BUO results in cost-effective maintenance of renal function and of renal parenchymal volume at a mean follow-up of 2 years; however, only 28% of patients fulfilled the 1-year criterion for RS indwell time.

A Review of the Recommendations and Strength of Evidence for Clinical Practice Guidelines on the Management of Small Renal Masses.

Introduction: With the rise in the detection of incidental small renal masses (SRM), the management paradigm for these patients has become an issue of increasing concern. We aim to identify areas of consensus, controversy, and opportunities for improvement among recently published guidelines and assess the strength of evidence for the management of SRMs. Methods: We reviewed practice guidelines for SRMs promulgated by the American Urological Association, European Association of Urology, National Comprehensive Cancer Network, American Society of Clinical Oncology, European Society for Medical Oncology, and the Chinese Society of Clinical Oncology. Levels of evidence and strength of recommendations for evaluation, management and follow-up were analyzed with regard to consensus, conflict, and neglect. Results: There is consensus among guidelines for the initial evaluation and treatment of SRMs; however, discrepancies exist with regard to indications for active surveillance, thermal ablation, and timing/method of follow-up after treatment. Routine renal mass biopsy is not recommended by any guideline. Overwhelmingly, guideline statements are based on low to moderate levels of evidence; only 23% of the reviewed guidelines were based on high-level evidence, 38% based on moderate-level, and 39% on low-level evidence or expert opinion. Conclusions: Despite all six guidelines sharing a consensus on most management topics regarding SRMs, the ongoing lack of high-level evidence precludes gold standard recommendations in the areas of diagnosis, treatment, and follow-up. More high-quality studies are needed to develop a stronger, data-supported universal guideline for the management of SRMs.

Porcine Bladder Replacement with a Bilayer Silk Fibroin Enhanced Prosthetic Reservoir: A Feasibility Study.

Introduction: The creation of synthetic reservoirs for bladder replacement has been limited by challenges of interfacing synthetic materials and native tissue. We sought to overcome this challenge by utilizing a novel bilayer silk fibroin scaffold (BLSF) as an intermediary toward the development of an acellular prosthetic reservoir. Methods: Under institutionally approved protocols, 3D-printed reservoirs were implanted in six juvenile female pigs after cystectomy. BLSF was attached to the in situ prosthetic reservoir serving as an intermediary to native ureteral and urethral tissue anastomoses. Our first protocol allowed four pigs to be survived up to 7 days, and the second protocol allowed two pigs to be survived for up to 1 year. At the first sign of functional decline or the end of the study period, the animals were euthanized, and kidneys, ureters, prosthetic bladder, and urethra were harvested en bloc for histopathology analysis. Results: The first two pigs had anastomotic urine leaks because of design flaws resulting in early termination. The third pig had acute renal failure resulting in early termination. The artificial bladder design was modified in subsequent iterations. The fourth pig survived for 7 days and, upon autopsy, had intact urethral and ureteral anastomoses. The fifth and sixth pigs survived for 11 and 12 weeks, respectively, before they were sacrificed because of failure to thrive. One animal developed an enteric fistula. The other animal had an intact anastomosis, and the BLFS was identified at the ureteral and urethral anastomoses on histopathologic analysis. Conclusions: Replacing the porcine bladder with a prosthetic bladder was achieved for up to 3 months, the second longest survival period for a nonbiologic bladder alternative. BLSF was used for the first time to create an interface between synthetic material and biologic tissue by allowing ingrowth of urothelium onto the acellular alloplastic bladder.

Drosophila melanogaster as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients.

Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper.

As in Real Estate, Location Is What Matters: A Case Report of Transplant Ureteral Obstruction Due to an Inguinal Hernia.

BACKGROUND: Kidney allograft dysfunction is common and often reversible but can lead to allograft loss if not promptly evaluated. Transplant ureteral obstruction in an inguinal hernia is a rare cause of allograft dysfunction, but early recognition may prevent allograft loss. CASE PRESENTATION: We present a case of a man with acute kidney allograft dysfunction who received a deceased donor kidney transplant 6 years earlier for end-stage kidney disease secondary to polycystic kidney disease. Abdominal ultrasounds revealed hydronephrosis without full visualization of the transplant ureter. Abdominal computed tomography revealed moderate hydronephrosis of the transplant kidney due to obstructed herniation of the transplant ureter in a right inguinal hernia. A stent was inserted into the transplant ureter to prevent further allograft dysfunction and facilitate hernia repair. CONCLUSIONS: Transplant ureteral obstruction is a rare cause of acute kidney allograft dysfunction, and its detection can be challenging. The recognition of transplant ureteral obstruction is vital to timely management for preventing allograft loss.

CONTEXTE: Les dysfonctionnements des allogreffes rénales sont fréquents, quoique souvent réversibles. Ils peuvent toutefois mener à la perte du greffon s'ils ne sont pas décelés rapidement. En présence d'une hernie inguinale, la détection précoce de l'obstruction de l'uretère du greffon, une cause rare de ces troubles fonctionnels, peut prévenir la perte du rein greffé. PRÉSENTATION DU CAS: Nous exposons le cas d'un homme ayant reçu, six ans plus tôt, une greffe de rein provenant d'un donneur décédé pour soigner une insuffisance rénale terminale résultant d'une polykystose rénale. Le patient présentait un cas aigu de dysfonctionnement du greffon. L'échographie abdominale a révélé la présence d'une hydronéphrose sans que l'uretère soit complètement visible. La tomodensitométrie abdominale a quant à elle révélé une hydronéphrose modérée dans le rein transplanté due à l'obstruction de l'uretère dans l'hernie inguinale du côté droit. Une endoprothèse a été insérée dans l'uretère du greffon pour empêcher l'aggravation des troubles fonctionnels et pour faciliter la réparation herniaire. CONCLUSION: L'obstruction de l'uretère est une cause rare du dysfonctionnement aigu d'un rein transplanté, et sa détection peut représenter un véritable défi. Le diagnostic de ce type d'occlusion est crucial pour intervenir rapidement et ainsi prévenir la perte du greffon.

Neonicotinoid-induced pathogen susceptibility is mitigated by Lactobacillus plantarum immune stimulation in a Drosophila melanogaster model.

Pesticides are used extensively in food production to maximize crop yields. However, neonicotinoid insecticides exert unintentional toxicity to honey bees (Apis mellifera) that may partially be associated with massive population declines referred to as colony collapse disorder. We hypothesized that imidacloprid (common neonicotinoid; IMI) exposure would make Drosophila melanogaster (an insect model for the honey bee) more susceptible to bacterial pathogens, heat stress, and intestinal dysbiosis. Our results suggested that the immune deficiency (Imd) pathway is necessary for D. melanogaster survival in response to IMI toxicity. IMI exposure induced alterations in the host-microbiota as noted by increased indigenous Acetobacter and Lactobacillus spp. Furthermore, sub-lethal exposure to IMI resulted in decreased D. melanogaster survival when simultaneously exposed to bacterial infection and heat stress (37 °C). This coincided with exacerbated increases in TotA and Dpt (Imd downstream pro-survival and antimicrobial genes, respectively) expression compared to controls. Supplementation of IMI-exposed D. melanogaster with Lactobacillus plantarum ATCC 14917 mitigated survival deficits following Serratia marcescens (bacterial pathogen) septic infection. These findings support the insidious toxicity of neonicotinoid pesticides and potential for probiotic lactobacilli to reduce IMI-induced susceptibility to infection.

Probiotic Lactobacillus rhamnosus Reduces Organophosphate Pesticide Absorption and Toxicity to Drosophila melanogaster.

Organophosphate pesticides used in agriculture can pose health risks to humans and wildlife. We hypothesized that dietary supplementation with Lactobacillus, a genus of commensal bacteria, would reduce absorption and toxicity of consumed organophosphate pesticides (parathion and chlorpyrifos [CP]). Several Lactobacillus species were screened for toleration of 100 ppm of CP or parathion in MRS broth based on 24-h growth curves. Certain Lactobacillus strains were unable to reach stationary-phase culture maxima and displayed an abnormal culture morphology in response to pesticide. Further characterization of commonly used, pesticide-tolerant and pesticide-susceptible, probiotic Lactobacillus rhamnosus strain GG (LGG) and L. rhamnosus strain GR-1 (LGR-1), respectively, revealed that both strains could significantly sequester organophosphate pesticides from solution after 24-h coincubations. This effect was independent of metabolic activity, as L. rhamnosus GG did not hydrolyze CP and no difference in organophosphate sequestration was observed between live and heat-killed strains. Furthermore, LGR-1 and LGG reduced the absorption of 100 µM parathion or CP in a Caco-2 Transwell model of the small intestine epithelium. To determine the effect of sequestration on acute toxicity, newly eclosed Drosophila melanogaster flies were exposed to food containing 10 µM CP with or without supplementation with live LGG. Supplementation with LGG simultaneously, but not with administration of CP 3 days prior (prophylactically), mitigated CP-induced mortality. In summary, the results suggest that L. rhamnosus may be useful for reducing toxic organophosphate pesticide exposure via passive binding. These findings could be transferable to clinical and livestock applications due to affordability and practical ability to supplement products with food-grade bacteria. IMPORTANCE: The consequences of environmental pesticide pollution due to widespread usage in agriculture and soil leaching are becoming a major societal concern. Although the long-term effects of low-dose pesticide exposure for humans and wildlife remain largely unknown, logic suggests that these chemicals are not aligned with ecosystem health. This observation is most strongly supported by the agricultural losses associated with honeybee population declines, known as colony collapse disorder, in which pesticide usage is a likely trigger. Lactobacilli are bacteria used as beneficial microorganisms in fermented foods and have shown potentials to sequester and degrade environmental toxins. This study demonstrated that commonly used probiotic strains of lactobacilli could sequester, but not metabolize, organophosphate pesticides (parathion and chlorpyrifos). This Lactobacillus-mediated sequestration was associated with decreased intestinal absorption and insect toxicity in appropriate models. These findings hold promise for supplementing human, livestock, or apiary foods with probiotic microorganisms to reduce organophosphate pesticide exposure.

Novel Methods of Determining Urinary Calculi Composition: Petrographic Thin Sectioning of Calculi and Nanoscale Flow Cytometry Urinalysis.

Accurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected during surgery subsequently underwent petrographic thin sectioning with polarized and fluorescent microscopy. Fluorescently labeled bisphosphonate probes (Alendronate-fluorescein/Alendronate-Cy5) were developed for nanoscale flow cytometry to enumerate nanocrystals that bound the fluorescent probes. Petrographic sections of stones were also imaged by fluorescent and polarized light microscopy with composition analysis correlated to alendronate +ve nanocrystal counts in corresponding urine samples. Urine samples from patients with Ca(2+) and Mg(2+) based calculi exhibited the highest alendronate +ve nanocrystal counts, ranging from 100-1000 nm in diameter. This novel urine based assay was in agreement with composition determined by petrographic thin sections with Alendronate probes. In some cases, high alendronate +ve nanocrystal counts indicated a Ca(2+) or Mg(2+) composition, as confirmed by petrographic analysis, overturning initial spectrophotometric diagnosis of stone composition. The combination of nanoscale flow cytometry and petrographic thin sections offer an alternative means for determining stone composition. Nanoscale flow cytometry of alendronate +ve nanocrystals alone may provide a high-throughput means of evaluating stone burden.