Ghrelin enhances tubular magnesium absorption in the kidney.

Osteoporosis after bariatric surgery is an increasing health concern as the rate of bariatric surgery has risen. In animal studies mimicking bariatric procedures, bone disease, together with decreased serum levels of Ca2+, Mg2+ and the gastric hormone Ghrelin were described. Ghrelin regulates metabolism by binding to and activating the growth hormone secretagogue receptor (GHSR) which is also expressed in the kidney. As calcium and magnesium are key components of bone, we tested the hypothesis that Ghrelin-deficiency contributes to osteoporosis via reduced upregulation of the renal calcium channel TRPV5 and the heteromeric magnesium channel TRPM6/7. We expressed GHSR with TRPV5 or TRPM6/7 channel in HEK293 cells and treated them with purified Ghrelin. Whole-cell current density was analyzed by patch-clamp recording. Nephron-specific gene expression was performed by tubular microdissection followed by qPCR in wild-type (WT) mice, and immunofluorescent imaging of GHSR-eGFP mice. Tubular magnesium homeostasis was analyzed in GHSR-null and WT mice at baseline and after caloric restriction. After Ghrelin exposure, whole-cell current density did not change for TRPV5 but increased for TRPM6/7 in a dose-dependent fashion. Applying the Ghrelin-mimetic (D-Trp7, Ala8,D-Phe10)-α-MSH (6-11) amide without and with the GHSR antagonist (D-Lys3)-GHRP6, we confirmed the stimulatory role of Ghrelin towards TRPM6/7. As GHSR initiates downstream signaling via protein kinase A (PKA), we found that the PKA inhibitor H89 abrogated TRPM6/7 stimulation by Ghrelin. Similarly, transfected Gαs, but not the Gαs mutant Q227L, nor Gαi2, Gαq, or Gα13 upregulated TRPM6/7 current density. In microdissected TALs and DCTs similar levels of GHSR mRNA were detected. In contrast, TRPM6 mRNA was expressed in the DCT and also detected in the TAL at 25% expression compared to DCT. Immunofluorescent studies using reporter GHSR-eGFP mice showed a strong eGFP signal in the TAL but surprisingly displayed no eGFP signal in the DCT. In 3-, 6-, and 9-month-old GHSR-null and WT mice, baseline serum magnesium was not significantly different, but 24-h urinary magnesium excretion was elevated in 9-month-old GHSR-null mice. In calorically restricted GHSR-null mice, we detected excess urinary magnesium excretion and reduced serum magnesium levels compared to WT mice. The kidneys from calorically restricted WT mice showed upregulated gene expression of magnesiotropic genes Hnf1b, Cldn-16, Cldn-19, Fxyd-2b, and Parvalbumin compared to GHSR-null mice. Our in vitro studies show that Ghrelin stimulates TRPM6/7 via GHSR and Gαs-PKA signaling. The murine studies are consistent with Ghrelin-GHSR signaling inducing reduced urinary magnesium excretion, particularly in calorically restricted mice when Ghrelin levels are elevated. This effect may be mediated by Ghrelin-upregulation of TRPM6 in the TAL and/or upregulation of other magnesiotropic genes. We postulate that rising Ghrelin levels with hunger contribute to increased renal Mg2+ reabsorption to compensate for lack of enteral Mg2+ uptake.

Nephronophthisis: a pathological and genetic perspective.

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most frequent genetic causes for kidney failure (KF) in children and adolescents. Over 20 genes cause NPHP and over 90 genes contribute to renal ciliopathies often involving multiple organs. About 15-20% of NPHP patients have additional extrarenal symptoms affecting other organs than the kidneys. The involvement of additional organ systems in syndromic forms of NPHP is explained by shared expression of most NPHP gene products in centrosomes and primary cilia, a sensory organelle present in most mammalian cells. This finding resulted in the classification of NPHP as a ciliopathy. If extrarenal symptoms are present in addition to NPHP, these disorders are defined as NPHP-related ciliopathies (NPHP-RC) and can involve the retina (e.g., with Senior-Løken syndrome), CNS (central nervous system) (e.g., with Joubert syndrome), liver (e.g., Boichis and Arima syndromes), or bone (e.g., Mainzer-Saldino and Sensenbrenner syndromes). This review focuses on the pathological findings and the recent genetic advances in NPHP and NPHP-RC. Different mechanisms and signaling pathways are involved in NPHP ranging from planar cell polarity, sonic hedgehog signaling (Shh), DNA damage response pathway, Hippo, mTOR, and cAMP signaling. A number of therapeutic interventions appear to be promising, ranging from vasopressin receptor 2 antagonists such as tolvaptan, cyclin-dependent kinase inhibitors such as roscovitine, Hh agonists such as purmorphamine, and mTOR inhibitors such as rapamycin.

A conditional gene expression system in Porphyromonas gingivalis for study of the secretion mechanisms of lipoproteins and T9SS cargo proteins.

The Gram-negative anaerobe, Porphyromonas gingivalis, is known to be a pathogen associated with chronic periodontitis. P. gingivalis possesses virulence factors such as fimbriae and gingipain proteinases. Fimbrial proteins are secreted to the cell surface as lipoproteins. In contrast, gingipain proteinases are secreted into the bacterial cell surface via the type IX secretion system (T9SS). The transport mechanisms of lipoproteins and T9SS cargo proteins are entirely different and remain unknown. Therefore, using the Tet-on system developed for the genus Bacteroides, we newly created a conditional gene expression system in P. gingivalis. We succeeded in establishing conditional expression of nanoluciferase and its derivatives for lipoprotein export, of FimA for a representative of lipoprotein export, and of T9SS cargo proteins such as Hbp35 and PorA for representatives of type 9 protein export. Using this system, we showed that the lipoprotein export signal, which has recently been found in other species in the phylum Bacteroidota, is also functional in FimA, and that a proton motive force inhibitor can affect type 9 protein export. Collectively, our conditional protein expression method is useful for screening inhibitors of virulence factors, and may be used to investigate the role of proteins essential to bacterial survival in vivo.

Physiology of a Forgotten Electrolyte-Magnesium Disorders.

Magnesium (Mg2+) is the second most common intracellular cation and the fourth most abundant element on earth. However, Mg2+ is a frequently overlooked electrolyte and often not measured in patients. While hypomagnesemia is common in 15% of the general population, hypermagnesemia is typically only found in preeclamptic women after Mg2+ therapy and in patients with ESRD. Mild to moderate hypomagnesemia has been associated with hypertension, metabolic syndrome, type 2 diabetes mellitus, CKD, and cancer. Nutritional Mg2+ intake and enteral Mg2+ absorption are important for Mg2+ homeostasis, but the kidneys are the key regulators of Mg2+ homeostasis by limiting urinary excretion to less than 4% while the gastrointestinal tract loses over 50% of the Mg2+ intake in the feces. Here, we review the physiological relevance of Mg2+, the current knowledge of Mg2+ absorption in the kidneys and the gut, the different causes of hypomagnesemia, and a diagnostic approach on how to assess Mg2+ status. We highlight the latest discoveries of monogenetic conditions causing hypomagnesemia, which have enhanced our understanding of tubular Mg2+ absorption. We will also discuss external and iatrogenic causes of hypomagnesemia and advances in the treatment of hypomagnesemia.

Autosomal dominant tubulointerstitial kidney disease: more than just HNF1ß.

Autosomal dominant tubulointerstitial kidney disease (ADTKD) refers to a group of disorders with a bland urinary sediment, slowly progressive chronic kidney disease (CKD), and autosomal dominant inheritance. Due to advances in genetic diagnosis, ADTKD is becoming increasingly recognized as a cause of CKD in both children and adults. ADTKD-REN presents in childhood with mild hypotension, CKD, hyperkalemia, acidosis, and anemia. ADTKD-UMOD is associated with gout and CKD that may present in adolescence and slowly progresses to kidney failure. HNF1ß mutations often present in childhood with anatomic abnormalities such as multicystic or dysplastic kidneys, as well as CKD and a number of other extra-kidney manifestations. ADTKD-MUC1 is less common in childhood, and progressive CKD is its sole clinical manifestation, usually beginning in the late teenage years. This review describes the pathophysiology, genetics, clinical characteristics, diagnosis, and treatment of the different forms of ADTKD, with an emphasis on diagnosis. We also present data on kidney function in children with ADTKD from the Wake Forest Rare Inherited Kidney Disease Registry.

N-Linked Glycosylation on Anthrax Toxin Receptor 1 Is Essential for Seneca Valley Virus Infection.

Seneca Valley virus (SVV) is a picornavirus with potency in selectively infecting and lysing cancerous cells. The cellular receptor for SVV mediating the selective tropism for tumors is anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein expressed in tumors. Similar to other mammalian receptors, ANTXR1 has been shown to harbor N-linked glycosylation sites in its extracellular vWA domain. However, the exact role of ANTXR1 glycosylation on SVV attachment and cellular entry was unknown. Here we show that N-linked glycosylation in the ANTXR1 vWA domain is necessary for SVV attachment and entry. In our study, tandem mass spectrometry analysis of recombinant ANTXR1-Fc revealed the presence of complex glycans at N166, N184 in the vWA domain, and N81 in the Fc domain. Symmetry-expanded cryo-EM reconstruction of SVV-ANTXR1-Fc further validated the presence of N166 and N184 in the vWA domain. Cell blocking, co-immunoprecipitation, and plaque formation assays confirmed that deglycosylation of ANTXR1 prevents SVV attachment and subsequent entry. Overall, our results identified N-glycosylation in ANTXR1 as a necessary post-translational modification for establishing stable interactions with SVV. We anticipate our findings will aid in selecting patients for future cancer therapeutics, where screening for both ANTXR1 and its glycosylation could lead to an improved outcome from SVV therapy.

Promising results after hemi-shoulder arthroplasty using pyrolytic carbon heads in young and middle-aged patients.

INTRODUCTION: The objective of this prospective cohort study was the assessment of short-term outcome results of shoulder hemiarthroplasty (HA) using pyrolytic carbon (PC) heads. PC has been introduced as a new material to avoid surgical revision due to glenoid erosion after HA. Glenoid erosion due to the use of metallic heads is known to reduce durability. HYPOTHESIS: HA using PC heads shows comparable or better radiographic and clinical outcome compared to the conventional HA using metallic heads in the short-term. PATIENTS AND METHODS: This study was conducted as a single center prospective cohort follow-up study including a total number of 16 consecutive HA with PC heads. Inclusion criteria were indication for HA, an intact rotator cuff, no proximal humeral fractures in patient's history and age>18years. Mean age at the time of arthroplasty was 52.8±10.8years. The mean follow-up was 24.3±8.1months. Baseline and follow-up Numeric Rating Scale (NRS), Constant Scores (CS), Range of Motion (ROM) and radiographs were assessed. RESULTS: At a mean follow-up of 24.3months the mean CS (p<0.001), mean NRS (p<0.001) and mean ROM (p<0.05) improved statistically significant. Subgroup analysis revealed no differences between subgroups (sex, age, diagnosis, and handedness). Survival rate was high (94.1%). One periprosthetic fracture occurred as the only complication during follow-up. Radiographs showed glenoid erosion in one case and subacromial space reduction in two cases. DISCUSSION: PC heads in HA show satisfying short-term results at a mean follow-up of two years, which are comparable to those of conventional HA. The clinical improvements were highly significant with good implant survival. However, long-term follow-up results are necessary, especially compared to conventional HA. LEVEL OF EVIDENCE: IV; observational therapeutic cohort study.

Cryptic species in the parasitic Amoebophrya species complex revealed by a polyphasic approach.

As critical primary producers and recyclers of organic matter, the diversity of marine protists has been extensively explored by high-throughput barcode sequencing. However, classification of short metabarcoding sequences into traditional taxonomic units is not trivial, especially for lineages mainly known by their genetic fingerprints. This is the case for the widespread Amoebophrya ceratii species complex, parasites of their dinoflagellate congeners. We used genetic and phenotypic characters, applied to 119 Amoebophrya individuals sampled from the same geographic area, to construct practical guidelines for species delineation that could be applied in DNA/RNA based diversity analyses. Based on the internal transcribed spacer (ITS) regions, ITS2 compensatory base changes (CBC) and genome k-mer comparisons, we unambiguously defined eight cryptic species among closely related ribotypes that differed by less than 97% sequence identity in their SSU rDNA. We then followed the genetic signatures of these parasitic species during a three-year survey of Alexandrium minutum blooms. We showed that these cryptic Amoebophrya species co-occurred and shared the same ecological niche. We also observed a maximal ecological fitness for parasites having narrow to intermediate host ranges, reflecting a high cost for infecting a broader host range. This study suggests that a complete taxonomic revision of these parasitic dinoflagellates is long overdue to understand their diversity and ecological role in the marine plankton.

Greater activity, better range of motion and higher quality of life following unicompartmental knee arthroplasty: a comparative case-control study.

PURPOSE: The purpose of this study was to provide a matched cohort comparison of clinical and functional outcome scores, range of motion and quality of life following unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). The hypothesis was that patients receiving UKA report better results than comparable patients who receive conventional TKA. METHODS: Clinical and functional results of 35 patients with medial end-stage osteoarthritis who had received a fixed-bearing UKA were compared with the results of 35 matched patients who had received a TKA from the same manufacturer by the same surgeon. Outcome scores were measured before surgery and at final follow-up using Tegner Activity Scale (TAS), range of motion (ROM) and Short Form 36 Health Survey (SF-36). The Knee Society Score (KSS) was assessed at final follow-up. The mean observation period was 2.3 years in both groups. RESULTS: The preoperative knee scores had no statistically significant differences between the two groups. Postoperatively, however, UKAs performed significantly better regarding TAS and ROM (4 vs. 3 and 118.4 vs. 103.7, respectively). The results of the SF-36 showed significantly better results for the UKA group in the mental component summary score and in the subscale of social function. CONCLUSIONS: The present study suggests that UKA is associated with higher activity level, higher quality of life, and greater ROM when compared with TKA on comparable patients. Prolonged clinical follow-up in a larger patient cohort with a randomised-controlled study design would be beneficial to confirm these findings. LEVEL OF EVIDENCE: III.

Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus.

Recently, the use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of the cellular receptors for the protective antigen secreted by Bacillus anthracis, has been identified as the high-affinity cellular receptor for SVV. Here, we report the structure of the SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates the outer surface of the SVV capsid and interacts with the surface-exposed BC loop and loop II of VP1, "the puff" of VP2 and "the knob" of VP3. Comparison of the receptor-bound capsid structure with the native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting the role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that the capsid footprint on the receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining the exquisite selectivity of SVV for ANTXR1.

Mercury Intoxication as a Rare Cause of Membranous Nephropathy in a Child.

In adults, membranous nephropathy is the second most common cause of nephrotic syndrome. In contrast, minimal change disease and focal segmental glomerulosclerosis constitute the most common forms of nephrotic syndrome in children, while membranous nephropathy accounts for <5% of cases. In adults, causes of membranous nephropathy include autoantibodies directed against phospholipase A2 receptor and thrombospondin type 1 containing 7A, various infections, environmental toxicities, autoimmune disorders, malignancies, and other secondary forms. The most common causes of secondary membranous nephropathy in children are infections, autoimmune diseases, and neoplasia. We discuss an unusual presentation of new-onset membranous nephropathy due to mercury toxicity in a 14-year-old male with reflux nephropathy. This case underscores the importance of a high index of suspicion for uncommon causes of nephrotic syndrome in pediatric patients with membranous nephropathy.

Prospective Pilot Evaluation of Radiologists and Computer-aided Pulmonary Nodule Detection on Ultra-low-Dose CT With Tin Filtration.

PURPOSE: The aim of this study was to evaluate the ability of computer-aided detection (CAD) and human readers to detect pulmonary nodules ≥5 mm using 100 kV ultra-low-dose computed tomography (ULDCT) utilizing a tin filter. MATERIALS AND METHODS: After informed consent, 55 patients prospectively underwent standard-dose chest CT (SDCT) using 120 kV followed by ULDCT using 100 kV/tin. Reference nodules ≥5 mm were identified by a thoracic radiologist using SDCT. Four thoracic radiologists marked detected nodules on SDCT and ULDCT examinations using a dedicated computer workstation. After a 6-month memory extinction, readers were shown the same ULDCT cases with all CAD markings as well as their original detections, and characterized CAD detections as true positive or false positive. RESULTS: Volume CT Dose index (CTDIvol) for SDCT and ULDCT were 5.3±2 and 0.4±0.2 mGy (P<0.0001), respectively. Forty-five reference nodules were detected in 30 patients. Reader sensitivity varied widely but similarly for SDCT (ranging from 45% to 87%) and ULDCT (45% to 83%). CAD sensitivity was 76% (34/45) for SDCT and 71% (32/45) for ULDCT. After CAD, reader sensitivity substantially improved by 19% and 18% for 2 readers, and remained nearly unchanged for the other 2 readers (0% and 2%), despite reader perception that many more nodules were identified with CAD. There was a mean of 2 false-positive CAD detections/case. CONCLUSIONS: ULDCT with 100 kV/tin reduced patient dose by over 90% without compromising pulmonary nodule detection sensitivity. CAD can substantially improve nodule detection sensitivity at ULDCT for some readers, maintaining interobserver performance.

Taxonomic assignment of the benthic toxigenic dinoflagellate Gambierdiscus sp. type 6 as Gambierdiscus balechii (Dinophyceae), including its distribution and ciguatoxicity.

Recent molecular phylogenetic studies of Gambierdiscus species flagged several new species and genotypes, thus leading to revitalizing its systematics. The inter-relationships of clades revealed by the primary sequence information of nuclear ribosomal genes (rDNA), however, can sometimes be equivocal, and therefore, in this study, the taxonomic status of a ribotype, Gambierdiscus sp. type 6, was evaluated using specimens collected from the original locality, Marakei Island, Republic of Kiribati; and specimens found in Rawa Island, Peninsular Malaysia, were further used for comparison. Morphologically, the ribotype cells resembled G. scabrosus, G. belizeanus, G. balechii, G. cheloniae and G. lapillus in thecal ornamentation, where the thecal surfaces are reticulate-foveated, but differed from G. scabrosus by its hatchet-shaped Plate 2', and G. belizeanus by the asymmetrical Plate 3'. To identify the phylogenetic relationship of this ribotype, a large dataset of the large subunit (LSU) and small subunit (SSU) rDNAs were compiled, and performed comprehensive analyses, using Bayesian-inference, maximum-parsimony, and maximum-likelihood, for the latter two incorporating the sequence-structure information of the SSU rDNA. Both the LSU and SSU rDNA phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between Gambierdiscus sp. type 6 and G. balechii was monophyletic. As a result, the taxonomic status of Gambierdiscus sp. type 6 was revised, and assigned as Gambierdiscus balechii. Toxicity analysis using neuroblastoma N2A assay confirmed that the Central Pacific strains were toxic, ranging from 1.1 to 19.9 fg P-CTX-1 eq cell-1, but no toxicity was detected in a Western Pacific strain. This suggested that the species might be one of the species contributing to the high incidence rate of ciguatera fish poisoning in Marakei Island.

Histone Deacetylase Inhibitor Treatment Increases the Expression of the Plasma Membrane Ca2+ Pump PMCA4b and Inhibits the Migration of Melanoma Cells Independent of ERK.

Several new therapeutic options emerged recently to treat metastatic melanoma; however, the high frequency of intrinsic and acquired resistance among patients shows a need for new therapeutic options. Previously, we identified the plasma membrane Ca2+ ATPase 4b (PMCA4b) as a metastasis suppressor in BRAF-mutant melanomas and found that mutant BRAF inhibition increased the expression of the pump, which then inhibited the migratory and metastatic capability of the cells. Earlier it was also demonstrated that histone deacetylase inhibitors (HDACis) upregulated PMCA4b expression in gastric, colon, and breast cancer cells. In this study, we treated one BRAF wild-type and two BRAF-mutant melanoma cell lines with the HDACis, SAHA and valproic acid, either alone, or in combination with the BRAF inhibitor, vemurafenib. We found that HDACi treatment strongly increased the expression of PMCA4b in all cell lines irrespective of their BRAF mutational status, and this effect was independent of ERK activity. Furthermore, HDAC inhibition also enhanced the abundance of the housekeeping isoform PMCA1. Combination of HDACis with vemurafenib, however, did not have any additive effects on either PMCA isoform. We demonstrated that the HDACi-induced increase in PMCA abundance was coupled to an enhanced [Ca2+]i clearance rate and also strongly inhibited both the random and directional movements of A375 cells. The primary role of PMCA4b in these characteristic changes was demonstrated by treatment with the PMCA4-specific inhibitor, caloxin 1c2, which was able to restore the slower Ca2+ clearance rate and higher motility of the cells. While HDAC treatment inhibited cell motility, it decreased only modestly the ratio of proliferative cells and cell viability. Our results show that in melanoma cells the expression of both PMCA4b and PMCA1 is under epigenetic control and the elevation of PMCA4b expression either by HDACi treatment or by the decreased activation of the BRAF-MEK-ERK pathway can inhibit the migratory capacity of the highly motile A375 cells.

The plasma membrane Ca2+ pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells.

Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca2+ signaling is a well-known regulator of tumor progression, the crosstalk between Ca2+ signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca2+ ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi. The MEK inhibitor selumetinib-similarly to that of the BRAF-specific inhibitor-also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. The increased abundance of PMCA4b in the plasma membrane enhances [Ca2+ ]i clearance from cells after Ca2+ entry. Moreover we show that both vemurafenib treatment and PMCA4b overexpression induce marked inhibition of migration of BRAF mutant melanoma cells. Importantly, reduced migration of PMCA4b expressing BRAF mutant cells is associated with a marked decrease in their metastatic potential in vivo. Taken together, our data reveal an important crosstalk between Ca2+ signaling and the MAPK pathway through the regulation of PMCA4b expression and suggest that PMCA4b is a previously unrecognized metastasis suppressor.

Two-stage revision of prosthetic hip joint infections using antibiotic-loaded cement spacers: When is the best time to perform the second stage?

AIM: Managing periprosthetic joint infections remains a challenging task, and adequate treatment strategies seem to be mandatory to avoid irreversible damage of the affected joint and/or systemic complications. Two-stage revision arthroplasty includes removing all implants and subsequent implantation of an antibiotic-loaded cement spacer, followed by revision arthroplasty as the second stage. Although this procedure is well described in the literature, results remain unpredictable due to various clinical findings and the absence of prospective randomised trials. We analysed (1) mortality and (2) reinfection rates in a series of patients who underwent two-stage revision surgery for periprosthetic hip joint infections with antibiotic-augmented joint spacers. We maintained a special focus on the spacer retention period and its influence on outcome in order to determine the best time for second-stage surgery. PATIENTS AND METHODS: A consecutive series of 76 patients with native and periprosthetic hip joint infections and who underwent two-stage revision surgery with antibiotic-loaded cement spacers were studied between 2005 and 2010. The second-stage operation was performed when it was assumed that infection was eradicated. The further operative procedure depended upon intra-operative findings (frozen section, local status). RESULTS: Mean implant-free period with the antibiotic-loaded spacer in situ was 12.6 weeks. Spacer re-implantation was necessary in 13 cases due to positive signs of acute infection in the frozen section and suspect intra-operative findings. Eight patients were not operated for a second time in the investigated time period due to poor general condition. In 40 patients, the spacer retention period was four to 11 weeks: 11 weeks for 23. We observed a significantly higher proportion of women free from reinfection in the four to 11-week group than in patients with the shorter or longer period. CONCLUSION: According to our findings, the optimal timing for second-stage surgery as a second-stage procedure is between four and 11 weeks. A significantly optimal reinfection rate was seen in patients undergoing revision arthroplasty within that time frame, and 90% of those patients remained infection free until final follow-up.

Autosomal dominant tubulointerstitial kidney disease: diagnosis, classification, and management--A KDIGO consensus report.

Rare autosomal dominant tubulointerstitial kidney disease is caused by mutations in the genes encoding uromodulin (UMOD), hepatocyte nuclear factor-1ß (HNF1B), renin (REN), and mucin-1 (MUC1). Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Juvenile Hyperuricemic Nephropathy (FJHN)', or 'Uromodulin-Associated Kidney Disease (UAKD)' for UMOD-related diseases and 'MCKD type 1' for the disease caused by MUC1 mutations. The multiplicity of these terms, and the fact that cysts are not pathognomonic, creates confusion. Kidney Disease: Improving Global Outcomes (KDIGO) proposes adoption of a new terminology for this group of diseases using the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' (ADTKD) appended by a gene-based subclassification, and suggests diagnostic criteria. Implementation of these recommendations is anticipated to facilitate recognition and characterization of these monogenic diseases. A better understanding of these rare disorders may be relevant for the tubulointerstitial fibrosis component in many forms of chronic kidney disease.