Evolving Approach in Nephron-Sparing Surgery: Has Anything Changed from Open Surgery to Laparoscopy?

OBJECTIVE: This study aimed to provide valuable insights into the comparative efficacy of different surgical approaches for nephron-sparing surgery (NSS) and contribute to the existing literature in this field. MATERIALS AND METHODS: This study included patients who underwent NSS for small renal masses between January 2016 and March 2024. A total of 97 patients (41 in the open approach group, 56 in the laparoscopic approach group) with demographic, radiological, intraoperative, renal functional, and oncological follow-up data were included. Three different anatomical scoring systems (R.E.N.A.L. nephrometry score, PADUA score and C-index) were utilised to assess tumour location and estimate proximity to the hilum and collecting system. RESULTS: In the open nephron-sparing surgery (ONSS) and laparoscopic nephron-sparing surgery (LNSS) groups, the mean kidney tumour diameters (SD) were 5.20 ± 2.30 and 4.90 ± 2.10, which were similar in both surgical method groups (p = 0.061). However, tumours treated with ONSS had significantly more adverse morphometric features (p < 0.05). For ONSS and LNSS groups, the mean R.E.N.A.L. nephrometry scores (SD) were 6.15 ± 2.04 and 5.2 ± 1.4 (p = 0.032), respectively; The mean PADUA scores (SD) were 7.46 ± 1.14 and 6.8 ± 1.0 (p = 0.049), respectively; And the mean C-index (SD) scores were 1.39 ± 0.4 and 1.37 ± 0.5 (p = 0.062), respectively. No significant differences were found in the mean tumour diameter (cm) (Inter Quantile Range (IQR)) distribution of both groups (p = 0.058). Despite the slight increase in transfusion rate in the LNSS group, estimated blood loss (EBL), transfusion rates, and length of hospital stay were similar in both groups. CONCLUSIONS: Although LNSS does not appear superior in terms of intraoperative blood loss, length of hospital stay and transfusion rate, it provides comparable long-term outcomes to ONSS. Our study suggests that when matched with nephrometry scores, LNSS can achieve similar outcomes to ONSS.

[Application value of domestic single-port robot in nephron sparing surgery].

Objective: To explore the application value of the domestic precision ®single-port robotic system in nephron sparing surgery. Methods: The clinical data of patients with renal masses underwent nephron sparing surgery using the domestic precision ®single-port robotic system at the PLA General Hospital, Gulou Hospital Affiliated to Nanjing University School of Medicine, Zhongnan Hospital of Wuhan University and the First Affiliated Hospital of Nanchang University from September to November 2023 were retrospectively included. Perioperative clinical data, pathological examination results, and postoperative complications were summarized. Results: A total of 12 patients were included, including 8 males and 4 females, with 26-75 (56±16) years. Body mass index (BMI) was (25.1±2.7) kg/m2. There were 6 cases on the left side and 6 case on the right side. The surgical approach was transabdominal in 9 cases and retroperitoneal in 3 case. The maximum diameter of the lesions was (2.7±0.7) cm, the warm ischemia time [M (Q1, Q3)] was 19 (15, 26) minutes, the surgical time was 180 (149, 216) minutes, and the intraoperative blood loss was 50 (28, 100) ml. Postoperative visual analogue scale (VAS) was (2.9±1.5) points. Postoperative pathology revealed malignant renal clear cell carcinoma in 9 cases, with nuclear grading of 3 cases for Grade 1, 3 cases for Grade 2, and 3 cases for Grade 3. Eight cases of pathological TNM staging were pT1aN0M0 and 1 case was pT3aN0M0, with no cancer at the resection margin. Three cases showed benign renal vascular smooth muscle lipoma. There were no postoperative blood transfusions and no complications such as fever, urine leakage and poor wound healing. Conclusion: The prliminary experience reveals that the domestic precision ®single-port laparoscopic robotic system has good clinical application value in urological nephron sparing surgery.

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis.

PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

Nephron-Specific Lin28A Overexpression Triggers Severe Inflammatory Response and Kidney Damage.

The RNA-binding proteins LIN28A and LIN28B contribute to a variety of developmental biological processes. Dysregulation of Lin28A and Lin28B expression is associated with numerous types of tumors. This study demonstrates that Lin28A overexpression in the mouse nephrons leads to severe inflammation and kidney damage rather than to tumorigenesis. Notably, Lin28A overexpression causes inflammation only when expressed in nephrons, but not in the stromal cells of the kidneys, highlighting its cell context-dependent nature. The nephron-specific Lin28A-induced inflammatory response differs from previously described Lin28B-mediated inflammatory feedback loops as it is IL-6 independent. Instead, it is associated with the rapid upregulation of cytokines like Cxcl1 and Ccl2. These findings suggest that the pathophysiological effects of Lin28A overexpression extend beyond cell transformation. Our transgenic mouse model offers a valuable tool for advancing our understanding of the pathophysiology of acute kidney injury, where inflammation is a key factor.

Microplastics exposure disrupts nephrogenesis and induces renal toxicity in human iPSC-derived kidney organoids.

Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 µm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity.

Nephron specific ATP6AP2 knockout increases urinary excretion of fatty acids and decreases renal cortical megalin expression.

ATP6AP2 knockout in the renal nephron impairs receptor-mediated endocytosis, increasing urinary albumin and glucose excretion and impairing weight gain. Nonesterified fatty acids (NEFA) in urine are bound to albumin and reabsorbed in the proximal tubule through receptor-mediated endocytosis by the megalin-cubilin complex. We hypothesized that ATP6AP2 knockout increases urinary NEFA excretion through a reduction in megalin. Ten-week-old male C57BL/6 mice with nephron specific inducible ATP6AP2 knockout and noninduced controls were fed either normal diet (ND 12% fat) or high fat diet (HFD 45% fat) for 6 months. ATP6AP2 knockout significantly increased urine albumin:creatinine ratio in both ND and HFD fed mice while normalized urine NEFA concentration increased 489% and 259% in ND and HFD knockout mice compared to respective controls. Knockout decreased renal cortical megalin mRNA by 47% on ND and 49% on HFD while megalin protein expression decreased by 36% and 44% respectively. At the same time, markers of mTOR activity were increased while autophagy was impaired. Our results indicate that nephron specific ATP6AP2 knockout increases urinary NEFA excretion in the setting of impaired receptor-mediated endocytosis. Further investigation should determine whether ATP6AP2 contributes to obesity related ectopic lipid deposition in the proximal tubule.

Identification of countercurrent tubule-vessel arrangements in the early development of mouse kidney based on immunohistochemistry and computer-assisted 3D visualization.

Nephron loop-vessel countercurrent arrangement in the medulla provides the structural basis for the formation of concentrated urine. To date, the morphogenesis of it and relevant water and solutes transportation has not been fully elucidated. In this study, with immunohistochemistry for aquaporins (AQP) and Na-K-2Cl co-transporter (NKCC2), as well as 3D visualization, we noticed in embryonic day 14.5 kidneys that the countercurrent arrangement of two pairs of loop-vessel was established as soon as the loop and vessel both extended into the medulla. One pair happened between descending limb and ascending vasa recta, the other occurred between thick ascending limb and descending vasa recta. Meanwhile, the immunohistochemical results showed that the limb and vessel expressing AQP-1 such as descending thick and thin limb and descending vasa recta was always accompanied with AQP-1 negative ascending vasa recta or capillaries and thick ascending limb, respectively. Moreover, the thick ascending limb expressing NKCC2 closely contacted with descending vasa recta without expressing NKCC2. As kidney developed, an increasing number of loop-vessels in countercurrent arrangement extended into the interstitium of the medulla. In addition, we observed that the AQP-2 positive ureteric bud and their branches were separated from those pairs of tubule-vessels by a relatively large and thin-walled veins or capillaries. Thus, the present study reveals that the loop-vessel countercurrent arrangement is formed at the early stage of nephrogenesis, which facilitates the efficient transportation of water and electrolytes to maintain the medullary osmolality and to form a concentrated urine.

Paradoxes in magnesium transport in type 1 Bartter's syndrome and Gitelman's syndrome: a modeling analysis.

Type 1 Bartter's syndrome and Gitelman's syndrome are characterized by mutations in two key renal Na+ transporters, Na-K-2Cl cotransporter (NKCC2) and Na-Cl cotransporter (NCC). Since these two transporters play an important role in regulating magnesium (Mg2+) and calcium (Ca2+) transport in the kidney, significant alterations in the transport of these two electrolytes are observed in type 1 Bartter's syndrome and Gitelman's syndrome. In this study, we used our sex-specific computational models of renal electrolyte transport in rats to understand the complex compensatory mechanisms, in terms of alterations in tubular dimensions and ion transporter activities, that lead to Mg2+ and Ca2+ preservation or wasting in these two genetic disorders. Given the sexual dimorphism in renal transporter patterns, we also assessed how the magnitude of these alterations may differ between males and females. Model simulations showed that in type 1 Bartter's syndrome, nephron adaptations prevent salt wasting and favor Mg2+ preservation but not Ca2+, whereas in Gitelman's syndrome, those adaptations favor Ca2+ preservation over Mg2+. In addition, our models predicted that the compensatory alterations in tubular dimensions and ion transporter activities are stronger in females than in males.NEW & NOTEWORTHY Although changes in Ca2+ excretion in type 1 Bartter's syndrome and Gitelman's syndrome are well understood, Mg2+ excretion displays an interesting paradox. This computational modeling study provides insights into how renal adaptations in these two disorders impact Ca2+ and Mg2+ transport along different nephron segments. Model simulations showed that nephron adaptations favor Mg2+ preservation over Ca2+ in Bartter's syndrome and Ca2+ preservation over Mg2+ in Gitelman's syndrome and are stronger in females than in males.

[Clinicopathological characteristics and prognosis of multilocular cystic renal neoplasm of low malignant potential].

OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods. METHODS: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared. RESULTS: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence. CONCLUSION: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.

Regulating distal nephron functions and salt sensitivity.

This review highlights the molecular basis of salt sensitivity in hypertension, with a focus on the regulation of sodium transport in the distal nephron. Sodium reabsorption in this region is often linked to the actions of aldosterone, although in recent years numerous findings have been reported on the aldosterone-independent pathway of acquiring salt sensitivity by potassium deficiency or potassium loading. The key to this discussion is the interplay, through extracellular potassium concentration, between the first part of the tubules expressing the Na+-Cl- cotransporter (NCC) and the second part expressing the epithelial Na+ channel (ENaC). The molecular pathways such as with-no-lysine 1 (WNK)-STE20/SPS1-related proline-alanine-rich kinase (SPAK)/oxidative stress-responsive kinase 1 (OSR1) signaling, Kelch-like family member 3 (KLHL3)-cullin 3 (CUL3) complex, protein phosphatases, and mechanistic target of rapamycin complex 2 (mTORC2)-Nedd4L pathway are described as the mechanism by which salt sensitivity on blood pressure is acquired in response to changes in physiological conditions including potassium depletion or loading. This review highlights the potential for targeting these molecular pathways to develop novel therapeutic strategies for the treatment of salt-sensitive hypertension, the mechanism of which remains to be elucidated.

Highly parallel production of designer organoids by mosaic patterning of progenitors.

Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. One open question is the extent to which engineering control over culture conditions can guide organoids to specific compositions. Here, we extend a DNA "velcro" cell patterning approach, precisely controlling the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions that depend on initial progenitor cell composition. These include higher nephron and stromal cell representation in mosaic NP/UB organoids vs. NP-only organoids and a "goldilocks" initial cell ratio in mosaic organoids that optimizes the formation of proximal tubule structures.

Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL's histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.

Expression of L1 Cell Adhesion Molecule, a Nephronal Principal Cell Marker, in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a benign, reactive lesion seen predominantly in the urinary bladder and often associated with antecedent inflammation, instrumentation, or an operative history. Its histopathologic diversity can create diagnostic dilemmas and pathologists use morphologic evaluation along with available immunohistochemical (IHC) markers to navigate these challenges. IHC assays currently do not designate or specify NA's potential putative cell of origin. Leveraging single-cell RNA-sequencing technology, we nominated a principal (P) cell-collecting duct marker, L1 cell adhesion molecule (L1CAM), as a potential biomarker for NA. IHC characterization revealed L1CAM to be positive in all 35 (100%) patient samples of NA; negative expression was seen in the benign urothelium, benign prostatic glands, urothelial carcinoma (UCA) in situ, prostatic adenocarcinoma, majority of high-grade UCA, and metastatic UCA. In the study, we also used single-cell RNA sequencing to nominate a novel compendium of biomarkers specific for the proximal tubule, loop of Henle, and distal tubule (DT) (including P and intercalated cells), which can be used to perform nephronal mapping using RNA in situ hybridization and IHC technology. Employing this technique on NA we found enrichment of both the P-cell marker L1CAM and, the proximal tubule type-A and -B cell markers, PDZKI1P1 and PIGR, respectively. The cell-type markers for the intercalated cell of DTs (LINC01187 and FOXI1), and the loop of Henle (UMOD and IRX5), were found to be uniformly absent in NA. Overall, our findings show that based on cell type-specific implications of L1CAM expression, the shared expression pattern of L1CAM between DT P cells and NA. L1CAM expression will be of potential value in assisting surgical pathologists toward a diagnosis of NA in challenging patient samples.

Kidney volume-to-birth weight ratio as an estimate of nephron endowment in extremely low birth weight preterm infants.

In humans, nephrogenesis is completed by 32-36 weeks gestation, with a highly variable total number of nephrons, ranging from 200,000 to over 2 million. Premature birth disrupts the development and maturation of the kidneys, leading to a reduction in the final number of nephrons. Due to significant genetic variability in the number of nephrons among individuals, it is crucial to identify premature infants with fewer nephrons at birth as early as possible. These infants are more susceptible to developing renal failure with advancing age compared to those with a higher nephron endowment. Bedside ultrasound, an effective and non-invasive tool, is practical for identifying newborns with a lower nephron count. However, renal volume alone cannot reliably indicate the number of nephrons due to substantial variability at birth, influenced by gestational age when nephron maturation is incomplete. This variability in kidney volumes persists as newborns grow. In this observational study we hypothesize that the relationship between renal volume and birth weight may serve as an indicator of nephron endowment in premature infants with birth weight less than 1000 g. This finding could represent the basis for defining appropriate surveillance protocols and developing targeted therapeutic approaches.

Comparing ECIRS with MPCNL for Complex Renal Calculi: A Retrospective Single-Centre Study on Efficacy and Safety.

BACKGROUND: Kidney stones, a common urinary system ailment, often necessitate surgical intervention. Endoscopic combined intrarenal surgery (ECIRS) and multi-channel percutaneous nephron lithotripsy (MPCNL) are key modalities for treating complex renal stones, prompting the need for a comparative analysis to enhance clinical decision-making. METHODS: Patients undergoing surgical treatment for complex kidney stones from April 2018 to April 2022 were divided into the control (MPCNL) and observation (ECIRS) groups. Propensity score matching was used to balance baseline data, and t-tests and chi-square tests were employed to compare the perioperative indicators between the two groups. RESULTS: A total of 210 patients were enrolled in this study for pre-observational comparison, and they were divided into the control group (110 patients) and observation group (100 patients). Following matching, each group comprised 85 patients. Pre-observational comparison revealed significant differences between the groups in age, disease duration, and stone diameter (p < 0.05). However, after matching, baseline data comparison showed no statistically significant differences (p > 0.05). Surgery-related parameters, including operation time, intraoperative blood loss, postoperative activity duration and hospital stay, did not significantly differ between the groups (p > 0.05). The observation group exhibited a significantly higher stone retention-free rate after initial treatment compared with the control group (p < 0.05), although overall stone clearance rates did not significantly differ between the groups (p > 0.05). We found no significant differences in perioperative complications between the two groups (p > 0.05). Moreover, the observation group experienced significantly lower postoperative pain levels at 6, 24 and 48 h compared with the control group (p < 0.001). CONCLUSIONS: Conclusively, ECIRS and MPCNL are viable options for treating complex renal calculi, with similar operation times, complication rates and stone clearance rates. ECIRS may offer advantages including lower postoperative pain and higher initial stone clearance rates than MPCNL. However, large-scale studies with long follow-up times are needed for validation.

Aldosterone-independent regulation of K + secretion in the distal nephron.

PURPOSE OF REVIEW: Maintenance of plasma K + concentration within a narrow range is critical to all cellular functions. The kidneys are the central organ for K + excretion, and robust renal excretory responses to dietary K + loads are essential for survival. Recent advances in the field have challenged the view that aldosterone is at the center of K + regulation. This review will examine recent findings and propose a new mechanism for regulating K + secretion. RECENT FINDINGS: Local aldosterone-independent response systems in the distal nephron are increasingly recognized as key components of the rapid response to an acute K + load, as well as playing an essential role in sustained responses to increased dietary K + . The master kinase mTOR, best known for its role in mediating the effects of growth factors and insulin on growth and cellular metabolism, is central to these aldosterone-independent responses. Recent studies have shown that mTOR, particularly in the context of the "type 2" complex (mTORC2), is regulated by K + in a cell-autonomous fashion. SUMMARY: New concepts related to cell-autonomous K + signaling and how it interfaces with aldosterone-dependent regulation are emerging. The underlying signaling pathways and effectors of regulated K + secretion, as well as implications for the aldosterone paradox and disease pathogenesis are discussed.