Rehmannia glutinosa Libosch and Cornus officinalis Sieb herb couple ameliorates renal interstitial fibrosis in CKD rats by inhibiting the TGF-ß1/MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Herb couple Rehmannia glutinosa Libosch and Cornus officinalis Sieb (RC), originated from "Liuwei Dihuang Pill" which recorded in Key to Therapeutics of Children's Diseases. Traditionally, they have been used widely for their ability to nourish yin and energize the kidneys. Our previous study indicated that the RC could protect against adenine induced Chronic kidney disease (CKD) rats. Nevertheless, there is still no clear explanation of the mechanisms by which RC affects renal interstitial fibrosis in CKD rats. AIM OF THE STUDY: Current Work aims to explore the amelioration and potential mechanism of RC on renal interstitial fibrosis in CKD rats. MATERIALS AND METHODS: CKD rats were induced by adenine. Two weeks after administration, blood, urine, and kidney tissue were collected for biochemical analysis. Observing the physiological state of rats through the changes of rat body weight and renal index. The pro-inflammatory cytokines were measured by enzyme linked immunosorbent assay (ELISA), while renal tissue damage and fibrosis were assessed with Hematoxylin-eosin staining (H&E) and Masson's trichrome staining. In order to determine the levels of indicators and proteins associated with fibrosis signaling pathways, real time PCR (Rt-PCR), Western blot (WB), and immunofluorescence were employed. RESULTS: The renal interstitial fibrosis led to impaired cellular functions with increased the levels of Blood Urea Nitrogen (BUN), Urine protein (UP), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6), and Tumor Necrosis Factor alpha (TNF-α). and simultaneous up-regulated collagenⅠ(COL-1), fibronection (FN), α-smooth muscle actin (a-SMA), transforming growth factor-ß1 (TGF-ß1), c-Jun N-terminal kinase (JNK), p38 and extracellular regulated protein kinases (ERK), down-regulated the expression of the E-cadherin proteins. RC notably improved renal dysfunction in CKD rats as indicated by decreases in BUN, UP, and renal index. In addition, consistent with the morphological changes of renal tissue, renal interstitial fibrosis in CKD rats after RC intervention was significantly improved, mainly manifested by a decrease in the positive expression of COL-1, FN, and a-SMA, and increased levels of E-cadherin protein. Meanwhile, RC reduced the classical pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α in adenine-induced CKD rats. Additionally, RC administration also down-regulated TGF-ß1, JNK, p38 and ERK. CONCLUSION: In conclusion, RC may reduce inflammation in adenine induced CKD rats, improve extracellular matrix (ECM) components deposition, and diminish epithelial-mesenchymal transition (EMT) marker protein levels. Furthermore, RC intervention significantly reduces the release of inflammatory cytokines and inhibits the TGF-ß1/MAPK signaling pathway. Based on the results, RC might be useful in the treatment of adenine induced renal fibrosis.

Research progress in functional magnetic resonance imaging assessment of lupus nephritis kidney injury.

Lupus nephritis is one of the most common and severe complications of systemic lupus erythematosus and is also a major predictor of poor prognosis and mortality. Lupus nephritis has the characteristics of insidious onset, complex pathological types, rapid progression of organ damage, and easy recurrence. Currently, kidney damage in lupus nephritis is usually assessed based on urine analysis, renal biopsy, and glomerular filtration rates. However, they all have certain limitations, making it difficult to diagnose lupus nephritis early and assess its severity and progression. With the rapid development of functional magnetic resonance, multiple functional imaging techniques are expected to provide more useful information for the pathophysiological development, early diagnosis, progression, prognosis, and renal function evaluation of lupus nephritis. This article reviews the principle of multiple functional magnetic resonance imaging and the research status of evaluating renal function in lupus nephritis.

Excellent Response to Full-Dose 177 Lu-PSMA-617 RLT in Metastatic Castration-Resistant Prostate Cancer With Transplant Kidney : A Step Ahead.

ABSTRACT: 177 Lu-PSMA radioligand therapy (RLT) has shown very encouraging results in metastatic castrate-resistant prostate cancer (mCRPC) patients with acceptable adverse events. The adverse events of RLT are mainly limited to salivary glands and kidneys. However, there is dearth of available data of RLT in transplanted kidney patients with mCRPC. Here is a case of 68-year-old mCRPC patient with history of renal transplant who underwent 4 cycles of 177 Lu-PSMA-617 RLT (~7.4 GBq/cycle). Posttherapy serum creatinine and glomerular filtration rate remained stable along with excellent response and symptomatic improvement, thus demonstrating the safety of full dose of 177 Lu-PSMA in renal transplant patients.

Histologic and molecular features of antibody-mediated rejection.

PURPOSE OF REVIEW: This review aims to summarize the highlights from recent research that involved pathological and molecular analysis of kidney allografts. RECENT FINDINGS: As the research on antibody-mediated rejection (AMR) continues to evolve, studies are focused on identification through transcript studies of pathogenetic pathways involved in the development of AMR as well as refinement of diagnostic methods either by correlating Banff pathologic lesions with clinical and molecular data or by machine learning. Of note, the past year has generated high impact research that underscore the importance of pathologic and molecular correlations and detection of transcripts or gene sets that would aid prognostication. The studies involving refinement of pathologic criteria also highlight the continuous efforts to achieve diagnostic accuracy and standardization. SUMMARY: Research involving histologic and molecular characteristics that define AMR are central to identification and understanding of pathogenetic pathways and remain critical in the development of diagnostic criteria.

Renal sarcoidosis presenting with chronic kidney disease and hypercalcemia.

Sarcoidosis is a multisystem inflammatory disease that most frequently affects the lungs, lymph nodes, eyes, and skin. Renal involvement is clinically rare. We describe a 72-year-old male who presented with chronic kidney disease and elevated serum calcium and angiotensin-converting enzyme. Renal biopsy pathology showed chronic granulomatous interstitial nephritis. Renal function was significantly improved after glucocorticoid therapy. This case emphasizes that chronic kidney disease and hypercalcemia can be clues for renal sarcoidosis. Early renal biopsy and projective treatment is beneficial for renal outcome.

Long-term renal outcomes of patients with non-proliferative lupus nephritis.

BACKGROUND/AIMS: Although non-proliferative lupus nephritis (LN) (class I, II or V) has been considered as a less severe type of LN, data on long-term renal prognosis are limited. We investigated the long-term outcomes and prognostic factors in non-proliferative LN. METHODS: We retrospectively reviewed patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V, or II + V by kidney biopsy from 1997 to 2021. A poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2. RESULTS: We included 71 patients with non-proliferative LN (class I = 4; class II = 17; class V = 48; class II+V = 2), and the overall rate of poor renal outcomes was 29.6% (21/71). The univariate analysis indicated that older age, low eGFR at 6 or 12 months, failure to reach complete remission at 6 months, and LN chronicity score > 4 or activity score > 6 were significantly associated with poor renal outcomes. The multivariate analysis revealed that low eGFR at 6 months (HR 0.971, 95% CI 0.949-0.991; p = 0.014) was significantly associated with poor renal outcomes. CONCLUSION: Poor renal outcomes occurred in approximately 30% of patients with non-proliferative LN after long-term follow-up. More active management may be needed for non-proliferative LN, especially for patients with eGFR < 60 mL/ min/1.73 m2 at 6 months follow-up after LN diagnosis.

Metanephric adenoma diagnosed on biopsy in an infant: a case report.

BACKGROUND: Metanephric adenoma is a rare benign renal tumor of the kidney, uncommonly observed in children. It is often misdiagnosed preoperatively as a malignant neoplasm, leading to an unnecessary nephrectomy. The challenge is to make the right diagnosis preoperatively and therefore manage it with conservative surgery. We report a case of a child with metanephric adenoma who underwent nephron-sparing surgery. CASE PRESENTATION: A renal tumor was discovered fortuitously in an 18-month-old Caucasian girl with several congenital malformations. Investigations showed a 28 × 27 × 27 mm left renal mass centrally located, well defined, nonvascularized, with no calcifications and which compressed the adjacent renal tissue. Furthermore, there were no signs of metastasis. The decision of a multidisciplinary meeting was to perform a computed tomography (CT)-scan-guided biopsy. Histologic examination concluded it was a metanephric adenoma. We performed a left open partial nephrectomy via a flank retroperitoneal incision. The final histopathological examination confirmed the diagnosis. The postoperative course was uneventful. CONCLUSION: Preoperative diagnosis of metanephric adenoma is challenging. Because of the high probability of unnecessary radical nephrectomy, preoperative biopsy can be safe and determining to guide a more conservative approach so nephron-sparing surgery can be performed.

Gentisic acid mitigates gentamicin-induced nephrotoxicity in rats.

The current investigation was considered to evaluate the beneficial effects of gentisic acid (GA) on gentamicin (GEN)-induced nephrotoxicity in rat kidneys through assessment of oxidative stress, inflammatory cytokines, and histopathological changes. Rats were split into five equal groups. Rats were treated with GA (25, 50, and 100 mg/kg/day, p.o.) for 14 consecutive days and GEN (100 mg/kg, i.p.) was administrated from day 8 to day 14 of the experiment. On the 15th day, blood samples were collected to determine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), blood urea nitrogen (BUN), and creatinine (Cr) levels. Malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß), and nitric oxide (NO) levels and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were assessed in the renal tissue. Histopathological evaluations were done to confirm the biochemical results. GEN increased the levels of NGAL, KIM-1, BUN, and Cr in serum as well as MDA, NO, GSH, TNF-α, and IL-1ß in renal tissue. Moreover, GEN administration reduced the activity of CAT, SOD, and GPx in renal tissue. Nonetheless, the administration of GA before and alongside GEN mitigated these deleterious effects. In conclusion, GA has a beneficial effect on biochemical, inflammatory, and oxidative stress indices against GEN-induced nephrotoxicity.

Importance of Follow-Up Biopsies in the Prediction of Renal Allograft Survival Following Polyomavirus-Associated Nephropathy.

OBJECTIVES: Allograft biopsy is the gold standard for diagnosing polyomavirus-associated nephropathy. We aimed to establish the effects of histopathologic findings proposed by the Banff Polyomavirus Working Group on graft outcome. We also aimed to understand the clinical importance of follow-up biopsies for patients with polyomavirus-associated nephropathy. MATERIALS AND METHODS: Our study included 22 patients with polyomavirus-associated nephropathy. All biopsies were classified according to the latest Banff Polyomavirus Working Group classification. Follow-up biopsies of all patients were evaluated in detail. RESULTS: The mean interval between polyomavirus-associated nephropathy and transplant was 10 ± 1.6 months. Of 22 patients, biopsy revealed stage 1 in 3 (13.6%), stage 2 in 17 (77.3%), and stage 3 in 2 patients (9.1%). Fourteen patients (63.6%) had polyomavirus viral load 3, 5 (22.7%) had polyomavirus viral load 2, and 3 had polyomavirus viral load 1. Among patients included in analyses, 18.2% had antibody-mediated rejection and 27.2% had T-cell-mediated rejection simultaneously with polyomavirus-associated nephropathy. Graft loss increased with increasing polyomavirus-associated nephropathy class and polyomavirus viral load (P = .015 and P = .002, respectively). The mean time of graft survival decreased with increasing degree of tubulitis, interstitial inflammation, plasma infiltration, and neutrophil infiltration. Patients with interstitial fibrosis, glomerular polyoma, and cortical plus medullar involvement showed earlier graft loss. Follow-up biopsies showed that diffuse interstitial fibrosis or persistent inflam-mation negatively influenced graft loss. CONCLUSIONS: The Banff Polyomavirus Working Group's schema significantly correlated with graft outcome. Early detection of polyomavirus-associated nephro-pathy and subsequent detection of persistent inflammation and interstitial fibrosis and tubular atrophy in follow-up biopsies and modification of immunosuppressive therapy can successfully prevent graft loss.

An uncommon mimicker of renal malignancy: IgG4-related disease.

BACKGROUND: Increased usage of cross sectional imaging for a variety of indications, in particular CT imaging, has led to an increased detection of renal and ureteric masses. Benign ureteric masses are rare, with 95% of identified tumours consisting of transitional cell carcinoma (TCC). IgG4-related disease is a recognised clinical systemic autoimmune, inflammatory condition with a propensity for multi-organ manifestation. Nephritis and pseudo-tumour formation can occur when kidneys are involved. Ureteric involvement is more rare. CASE PRESENTATION: Forty nine-year-old Korean male was found to have an incidental invasive renal pelvis mass during investigation for chronic back pain and fatigue. Appearance of the tumour was consistent with an invasive malignancy, and consensus from multidisciplinary meeting was to have the tumour removed. Procedure involved a prolonged open surgery with reconstruction of contralateral renal blood supply and was complicated by a long recovery process. Final histopathology confirmed IgG4 renal pseudo tumour diagnosis. CONCLUSION: IgG4-related disease is a rare but potentially morbid disease that can mimic various cancers, including lung, pancreas and renal malignancies. A high index of suspicion is required to accurately diagnose this condition, through a targeted history taking, examination and investigation which should include biopsies. Failing to do so may result in unnecessary procedures being performed and exposing a patient to its associated risks.

Nephrotoxicity induced by different diameters of sphere gold nanoparticles with special emphasis on the nephroprotective role of quercetin.

Background: Although, gold nanoparticles (GNPs) are attracting more and more attention due to their ease of synthesis, modification, and great potential value in biomedical applications, exhibited harmful effects on human health and other living species. Quercetin (Qur) clarifies diverse pharmacological effects, especially anti-inflammatory, antiapoptotic, and antioxidant ones. Aim: This study aimed to evaluate the probable nephrotoxicity induced by different diameters of sphere GNPs, as well as the nephroprotective role of Qur. Methods: A total of 54 healthy mature male albino rats were grouped and treated with or without sphere GNPs; 10, 20, and 50 nm and Qur (200 mg/kg b.wt.). The effects of GNPs and Qur were estimated through the collection of blood and kidney samples from euthanized rats and performed biochemical, histopathological, and immunohistochemical investigations. Results: In comparison between different diameters of GNPs, the 10 nm GNPs revealed more significant elevations in all renal function parameters: creatinine, urea, blood urea nitrogen, and uric acid followed by 20 nm then 50 nm. Pre-cotreatment with Qur decreased all renal functional values. Histopathologically, 10 nm revealed the most potent renal pathological changes represented in the renal cortex with cloudy swelling of renal tubules, hypercellularity of some glomeruli, severe congestion of renal blood vessels, focal inter tubular edema, and vascular endotheliosis (degeneration of endothelium). In addition, the renal medulla revealed perivascular inflammatory cellular infiltration, perivascular fibrosis, intra tubular glycogen deposition, and casts deposition of mainly cellular casts. On the other hand, the Qur treatment ameliorated most of these pathological changes. Conclusion: The size of GNPs is pivotal in their pathological effect on renal tissues where the small-sized GNPs; 10 nm have more potent cytotoxic, inflammatory, and apoptotic effects rather than the larger ones. Otherwise, Qur clarified a significant mitigating role against the nephrotoxicity of the GNPs.

UCP1 alleviates renal interstitial fibrosis progression through oxidative stress pathway mediated by SIRT3 protein stability.

BACKGROUND: Renal interstitial fibrosis is a common pathway for the progressive development of chronic renal diseases (CKD) with different etiology, and is the main pathological basis leading to end-stage renal disease. Although the current research on renal interstitial fibrosis is gradually deepening, the diagnosis and treatment methods are still very lacking. Uncoupling protein 1 (UCP1) is a nuclear encoded protein in mitochondria inner membrane and plays an important role in regulating energy metabolism and mitochondrial homeostasis. However, the biological significance of UCP1 and potential regulatory mechanisms in the development of CKD remain unclear. METHODS: Unilateral ureteral obstruction (UUO) model was used to construct the animal model of renal fibrosis, and TGF-ß1 stimulation of HK2 cells was used to construct the vitro model of renal fibrosis. UCP1 expression was detected by Western blot, immunoblot analysis and immunohistochemistry. UCP1 was upregulated by UCP1 overexpressing lentivirus and UCP1 agonist CL316243. Western blot and immunofluorescence were used to detect epithelial mesenchymal transition (EMT)-related markers, such as collagen I, fibronectin, antioxidant enzyme SOD2 and CAT. Reactive oxygen species (ROS) production was detected by ROS detection kit. SIRT3 knockdown was performed by siRNA. RESULTS: This study presents that UCP1 is significantly downregulated in patients with renal fibrosis and UUO model. Further studies discover that UCP1 overexpression and CL316243 treatments (UCP1 agonists) reversed EMT and extracellular matrix (ECM) accumulation in renal fibrosis models in vivo and in vitro. Simultaneously, UCP1 reduced the ROS production by increasing the stability of SIRT3. When SIRT3 was knocked down, the production of ROS decreased. CONCLUSIONS: Elevating the expression of UCP1 can inhibit the occurrence of oxidative stress by stabilizing SIRT3, thereby reducing EMT and ECM accumulation, and ultimately alleviating renal interstitial fibrosis. It will provide new instructions and targets for the treatment of CKD.

Learning more from the inter-rater reliability of interstitial fibrosis assessment beyond just a statistic.

Interstitial fibrosis assessment by renal pathologists lacks good agreement, and we aimed to investigate its hidden properties and infer possible clinical impact. Fifty kidney biopsies were assessed by 9 renal pathologists and evaluated by intraclass correlation coefficients (ICCs) and kappa statistics. Probabilities of pathologists' assessments that would deviate far from true values were derived from quadratic regression and multilayer perceptron nonlinear regression. Likely causes of variation in interstitial fibrosis assessment were investigated. Possible misclassification rates were inferred on reported large cohorts. We found inter-rater reliabilities ranged from poor to good (ICCs 0.48 to 0.90), and pathologists' assessments had the worst agreements when the extent of interstitial fibrosis was moderate. 33.5% of pathologists' assessments were expected to deviate far from the true values. Variation in interstitial fibrosis assessment was found to be correlated with variation in interstitial inflammation assessment (r2 = 32.1%). Taking IgA nephropathy as an example, the Oxford T scores for interstitial fibrosis were expected to be misclassified in 21.9% of patients. This study demonstrated the complexity of the inter-rater reliability of interstitial fibrosis assessment, and our proposed approaches discovered previously unknown properties in pathologists' practice and inferred a possible clinical impact on patients.

HYAL1 deficiency attenuates lipopolysaccharide-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice.

BACKGROUND: Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time. METHODS: BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked in vivo using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting. RESULTS: The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling. CONCLUSION: HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice.

Exploring hospital practice types and their impact on glomerular pathologic patterns: Insights from the largest kidney biopsy cohort in Thailand.

BACKGROUND: This study aims to investigate the influence of different kidney biopsy practices on the prevalence of glomerular pathologic patterns in the largest kidney biopsy registry in Thailand. METHODS: We conducted a retrospective review of kidney biopsy records from the period between 2000 and 2014. The records were obtained from 2 major institutions: King Chulalongkorn Memorial Hospital, a large university-based hospital, and the Kidney Center Bangkok Hospital, which provides pathology services to hospitals throughout Thailand. The study included native kidney biopsies from all provinces in Thailand, excluding paediatric patients, kidney transplant recipients, and cases of inadequate and repeated biopsies. Patient demographics, indications for biopsy, and final glomerular diagnoses were compared across different hospital practice settings: university (UVH), private (PVH) and public (PBH). RESULTS: A total of 5893 eligible native kidney biopsies were identified from a pool of 7005 biopsies conducted over a 15-year period in 25 provinces throughout Thailand. The 3 most common indications for biopsy were suspected kidney involvement in systemic lupus erythematosus (SLE) (29%), nephrotic syndrome (NS) (29%), and acute glomerulonephritis (AGN)/rapidly progressive glomerulonephritis (RPGN) (13%). The leading indication for biopsy differed across practice types, with suspected kidney involvement in SLE being the primary indication in UVH, while NS took precedence in both PBH and PVH practices. Notably, UVH performed fewer kidney biopsies for asymptomatic urinary abnormalities and diabetes-related indications compared with PVH and PBH. The leading glomerular diagnoses correlated with the biopsy indications, with lupus nephritis (LN) being the most common diagnosis in UVH and PBH practices, whiles immunoglobulin A nephropathy was the predominant diagnosis in PVH practice. CONCLUSION: Hospital practice types significantly impact the prevalence of glomerular pathologic diagnosis patterns in kidney biopsy data, highlighting the importance of considering this influence in epidemiological comparisons.

Partial versus radical nephrectomy for complex renal mass: multicenter comparative analysis of functional outcomes (Rosula collaborative group).

BACKGROUND: Utility of partial nephrectomy (PN) for complex renal mass (CRM) is controversial. We determined the impact of surgical modality on postoperative renal functional outcomes for CRM. METHODS: We retrospectively analyzed a multicenter registry (ROSULA). CRM was defined as RENAL Score 10-12. The cohort was divided into PN and radical nephrectomy (RN) for analyses. Primary outcome was development of de-novo estimated glomerular filtration rate (eGFR)<45 mL/min/1.73 m2. Secondary outcomes were de-novo eGFR<60 and ΔeGFR between diagnosis and last follow-up. Cox proportional hazards was used to elucidate predictors for de-novo eGFR<60 and <45. Linear regression was utilized to analyze ΔeGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year freedom from de-novo eGFR<60 and <45. RESULTS: We analyzed 969 patients (RN=429/PN=540; median follow-up 24.0 months). RN patients had lower BMI (P<0.001) and larger tumor size (P<0.001). Overall postoperative complication rate was higher for PN (P<0.001), but there was no difference in major complications (Clavien III-IV; P=0.702). MVA demonstrated age (HR=1.05, P<0.001), tumor-size (HR=1.05, P=0.046), RN (HR=2.57, P<0.001), and BMI (HR=1.04, P=0.001) to be associated with risk for de-novo eGFR<60 mL/min/1.73 m2. Age (HR=1.03, P<0.001), BMI (HR=1.06, P<0.001), baseline eGFR (HR=0.99, P=0.002), tumor size (HR=1.07, P=0.007) and RN (HR=2.39, P<0.001) were risk factors for de-novo eGFR<45 mL/min/1.73 m2. RN (B=-10.89, P<0.001) was associated with greater ΔeGFR. KMA revealed worse 5-year freedom from de-novo eGFR<60 (71% vs. 33%, P<0.001) and de-novo eGFR<45 (79% vs. 65%, P<0.001) for RN. CONCLUSIONS: PN provides functional benefit in selected patients with CRM without significant increase in major complications compared to RN, and should be considered when technically feasible.