Classification Criteria for Tubulointerstitial Nephritis With Uveitis Syndrome.

PURPOSE: To determine classification criteria for tubulointerstitial nephritis with uveitis (TINU). DESIGN: Machine learning of cases with TINU and 8 other anterior uveitides. METHODS: Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand eighty-three cases of anterior uveitides, including 94 cases of TINU, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% confidence interval 92.4, 98.6). Key criteria for TINU included anterior chamber inflammation and evidence of tubulointerstitial nephritis with either (1) a positive renal biopsy or (2) evidence of nephritis (elevated serum creatinine and/or abnormal urine analysis) and an elevated urine ß-2 microglobulin. The misclassification rates for TINU were 1.2% in the training set and 0% in the validation set. CONCLUSIONS: The criteria for TINU had a low misclassification rate and seemed to perform well enough for use in clinical and translational research.

A Multicenter Application of the 2018 Banff Classification for BK Polyomavirus-associated Nephropathy in Renal Transplantation.

BACKGROUND: With current immunosuppressive regimens, BK polyomavirus-associated nephropathy (BKPyVAN) is still a matter of concern. Stratification of patients at risk for allograft loss is of uttermost importance to guide treatment choice and assess prognosis. In 2018, the Banff working group proposed a classification scheme for the prognosis of BKPyVAN, but external application on independent cohorts is yet to be performed. We investigated how the 2018 Banff classification would perform in a multicenter cohort comprising 50 cases of biopsy-proven BKPyVAN compared to previously published classification systems. METHODS: We analyzed consecutive BKPyVAN cases from two Dutch university hospitals between 2002 and 2013, retrieved clinical data, and scored all biopsies according to the Banff 2018 classification, and as a comparison, 4 previously proposed BKPyVAN classification systems. We used estimated glomerular filtration rate trajectories and death-censored graft survival as primary endpoints. RESULTS: The 2018 Banff classification did not associate with estimated glomerular filtration rate decline or graft failure and performed only slightly better than the 4 previously proposed classifiers. Anti-human leukocyte antigen donor-specific antibodies (DSAs), especially in combination with ongoing biopsy-proven BKPyVAN on follow-up, did correlate with graft function and survival. Patients who were DSA+/BKPyVAN+ on follow-up had more inflammation at the baseline biopsy, which by itself was not associated with graft outcomes. CONCLUSIONS: Neither the 2018 Banff BKPyVAN classification nor previously published stratification systems could be applied to our multicenter patient cohort. Our data suggest that there might be a prognostic value for follow-up biopsies and DSA measurements to improve risk stratification after BKPyVAN, although prospective multicenter efforts with protocol measurements are needed to confirm this.

The beneficial effects of renin-angiotensin system inhibitors (RASI) on IgA nephropathy with tubulointerstitial lesions categorized by Oxford classification.

BACKGROUND: Global sclerosis has been reported as the risk factor of IgAN. In Oxford classification, global sclerosis was correlated with tubulointerstitial (T) lesions. Therefore, in patients with T lesions, renin-angiotensin system inhibitors (RASI) might be effective by decreasing glomerular hyperfiltration and hypertension. However, these beneficial effects of RASI have not been reported. METHODS: In this retrospective cohort study, we divided 87 IgAN patients with T1/2 lesions into two groups: RASI group (n = 47, treated with RASI) and APA group (n = 40, treated with anti-platelet agents). We analyzed the background of each group, the serial changes of blood pressure and the amount of proteinuria (U-Prot), progression to end-stage renal disease, and the risk factors for progression. RESULTS: After propensity score matching, 22 cases from each group were selected, and clinical and histological characteristics were similar. Serial changes of blood pressure had been significantly decreased in RASI group (p = 0.0029), but not in the APA group. Proteinuria was tended to decrease in RASI group, though it was not significant (1.14-0.47 g/gCre) and it was similar in APA group (0.95-0.85 g/gCre). 20 year renal survival rate was 59.5% in RASI group, whereas 21.3% in APA group (p = 0.0119). In multivariate Cox regression analysis, RASI was an independent factor to prevent from progression to ESRD (HR 5.91, p = 0.0039). CONCLUSION: RASI has shown a significant beneficial effect on histologically advanced IgAN patients with T lesions. These results are compatible with the previous studies that reported the beneficial effects of RASI on clinically advanced IgAN patients.

Assessment of KDIGO definitions in patients with histopathologic evidence of acute renal disease.

BACKGROUND AND OBJECTIVES: AKI is a clinical syndrome with various causes involving glomerular, interstitial, tubular, and vascular compartments of the kidney. Acute kidney disease (AKD) is a new concept that includes both AKI and the conditions associated with subacute decreases in GFR (AKD/non-AKI). This study aimed to investigate the correlation between AKI/AKD defined by clinical presentation and diffuse histologic criteria for acute abnormalities based on renal biopsy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All 303 patients who were histologically diagnosed as having acute tubular necrosis (ATN), acute tubulointerstitial nephritis, cellular crescentic GN, acute thrombotic microangiopathy, or complex lesions on renal biopsy from January 2009 to December 2011 were enrolled in the study. The 2012 Kidney Disease Improving Global Outcomes AKD/AKI definitions were applied to classify patients as follows: AKI, AKD/non-AKI, non-AKD, or unclassified. RESULTS: A total of 273 patients (90.1%) met the AKD criteria; 198 patients (65.3%) were classified as having AKI according to serum creatinine (SCr) and urine output criteria. The urine output criteria added 4.3% to the SCr criteria and reclassified 6.7% of the AKI cases into higher stages. Of patients with ATN on pathology, 79.2% met AKI criteria; this was a higher percentage than for those who had other individual pathologic lesions (50%-64%). The major cause of not being defined as having AKI was a slower SCr increase than that required by the definition of AKI (98, 93.3%). Patients with AKI had more severe clinical conditions and worse short-term renal outcome than those in the non-AKI group. CONCLUSIONS: Diffuse, acute abnormality defined by renal biopsy and AKI defined by clinical presentation are two different entities. Most patients who have diffuse acute histologic findings met the criteria for AKD, whereas only two thirds met the definition of AKI.

Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: what is in a name?

PURPOSE OF REVIEW: Chronic allograft nephropathy has fallen into disfavor as a morphologic term to describe parenchymal scarring in the renal allograft, with a recommendation that this be replaced by the more descriptive term 'interstitial fibrosis and tubular atrophy'. However, neither term addresses the underlying cause of the scarring. This review focuses on whether all interstitial fibrosis and tubular atrophy in the renal allograft has the same implications for long-term graft survival, and whether there are specific features of interstitial fibrosis and tubular atrophy that can be used to identify its underlying cause. RECENT FINDINGS: Results from a number of studies indicate that interstitial fibrosis and tubular atrophy, when associated with interstitial inflammation, is a strong predictor of graft loss, much more so than interstitial fibrosis and tubular atrophy alone. Most notably, findings from the multicenter Long-Term Deterioration of Kidney Allograft Function study, designed to identify the causes of late allograft dysfunction, showed interstitial inflammation in the areas of interstitial fibrosis and tubular atrophy (i-IF/TA) was predictive of reduced time to graft failure, even after adjustment for serum creatinine. In addition, the presence of i-IF/TA correlates with increased acute kidney injury gene transcripts. However, neither interstitial fibrosis and tubular atrophy nor i-IF/TA is associated with any specific cause of chronic graft injury. SUMMARY: Although (i-IF/TA), especially when widespread, is clearly associated with reduced renal allograft survival and molecular markers of active graft injury and repair, there is presently no reliable way, using either morphology alone, immunohistochemistry, or molecular techniques, to differentiate i-IF/TA (or interstitial fibrosis and tubular atrophy alone) resulting from different causes.

Alterações morfológicas e funcionais dos rins de cães com insuficiência renal crônica / Morphologic and functional alterations of the kidneys of dogs with chronic renal failure

Alterações morfológicas de 11 casos de cães com insuficiência renal foram caracterizadas e classificadas de acordo com os padrões estabelecidos pela Organização Mundial de Saúde para seres humanos. Glomerulonefrite esclerosante difusa foi diagnosticada em 82,0 por cento dos animais e nefrite intersticial crônica nos 18,0 por cento restantes. Os tipos e freqüência das lesões identificadas foram similares às encontradas na literatura para a insuficiência renal crônica.

Morphologic alterations of 11 cases of dogs with renal failure were characterized and classified according to the patterns established by the World Health Organization for human beings. Diffuse sclerosing glomerulonephritis was diagnosed in 82.0 percent of the animals and chronic interstitial nephritis in the remaining 18.0 percent. The types and frequencies of lesions were similar to the those noticed in the literature for chronic renal failure.

[Nephronophtisis]. / Néphronophtise.

Nephronophthisis is a chronic tubulo-interstitial nephritis which progress to terminal renal failure. It is an heterogeneous entity at the clinical as well as at the genetic level. There are three main clinical forms of nephronophtisis which have been associated with five gene defects. Juvenile nephronophtisis, the most frequent, progress to end stage renal failure before age 15. It is an autosomal recessive disease which is responsible for a urine concentration defect starting after age 2, failure to thrive and a progressive deterioration of renal function without signs of glomerular disease. Kidney size is normal. Histologic lesions concern tubular basement membranes which are thickened and multilayered or thinned. There is an associated interstitial fibrosis. Some children present with extrarenal symptoms: tapetoretinal degeneration (Senior-Loken syndrome), mental retardation, cerebellar ataxia, bone anomalies or liver involvement. Infantile nephronophtisis is a recessive autosomic tubulo-interstitial nephritis with cortical microcysts which progress to end stage renal failure before age 5. Adolescent nephronophtisis is a less frequent form of nephronophtisis. Medullary cystic disease is transmitted as an autosomic dominant trait. Clinical and histological signs are similar to nephronophthisis, but the disease progress later to terminal renal failure and is not accompanied by extra-renal symptoms. Several genes which are involved in nephronophtisis, encode proteins that localize in different cell compartments, in particular to the primary apical cilia, as it is the case for many other cystic kidney diseases.

Loratadina y nefritis intersticial aguda / Acute interstitial nephritis induced by loratadine

La loratadina en un antagonista de segunda generación de los receptores H1 de la histamina con mayor potencia antialergénica y asociada a menos efectos adversos que otros antihistamínicos. La nefritis intersticial es una causa de insuficiencia renal aguda generalmente inducida por drogas, y con menor frecuencia asociada a infecciones o sarcoidosis. Aunque el número de fármacos asociados a nefritis intersticial aguda es inmenso, nunca anteriormente había sido descrita la loratadina. Presentamos un caso de nefritis intersticial en un paciente que había recibido loratadina (10 mg/día) durante los diez días previos a su ingreso en nuestro hospital, por un cuadro de prurito diseminado. La sospecha inicial fue de glomerulonefritis rápidamente progresiva, por lo que se practicó biopsia renal y se inició tratamiento esteroideo (tres bolos de 500 mg, seguidos de 1 mg/kg/día de prednisona). La loratadina fue suspendida. Asistimos a una lenta aunque progresiva mejoría de función renal, y un mes más tarde la analítica (urea y creatinina) era normal y la hematuria y proteinuria habían desaparecido. Se inició pauta descendente de tratamiento esteroideo. Pensamos que se trata de un caso interesante dada su presentación clínica y la particularidad de no estar descrito con anterioridad

Loratadine is a second generation histamine H1 receptor antagonist, that has high potency antiallergic properties and is associated with low adverse effects compared with other antihistamines. Acute interstitial nephritis is a cause of acute renal failure that is most often induced by drugs or, less frequently, infection or sarcoidosis. Although the number of drugs associated with acute intersticial nephritis is too large, the antihistaminic loratadine have never been reported before. We report a case of an interstitial nephritis with acute renal failure that suggesting hypersensitivity reaction in a 77 old man who had received loratadine (10 mg/day) during ten days before his assesment to our hospital by diseminated pruritic syndrome. The initial suspect was rapidly progressive glomerulonephitis and renal biopsy was practice and treatment with corticosteroids were initiated (prednisone bolus of 500 mg three days and 1 mg/kg/day/later). The loratadine therapy was cessation. He exhibiting a slow and progressive improvement on renal function and one month later, urea and creatinine levels was normal and hematuria and proteinuria had disapeared. The corticosteroids therapy were progressive decreased until withdrawal. We think that this is an interesting case, basing in its clinical presentation and that it had never been reported before

Towards the identification of (a) gene(s) for autosomal dominant medullary cystic kidney disease.

Medullary cystic kidney disease (MCKD) belongs with nephronophthisis (NPH) in a group of inherited tubulo-interstitial nephritis, which has been referred to as the NPH-MCKD complex. Although MCKD and NPH share morphological features, they differ in several respects. The most common variant is recessive juvenile NPH, with onset in childhood and leading to end-stage renal disease (ESRD) within the 2nd decade of life; the most frequent extrarenal involvement is tapeto-retinal degeneration. MCKD is a dominant condition recognized in later life and leading to ESRD at the age of 50 years; hyperuricemia and gout can be associated features. The first sign of MCKD is polyuria; later, the clinical findings relate to renal insufficiency. Originally, NPH and MCKD were considered separate entities. Subsequently, it has been suggested that the two diseases were a single disorder due to the clinico-pathological identity. This unifying conception was later refuted due to the identification of MCKD dominant families. Recently, considerable insight has been gained into the genetics of the NPH-MCKD complex. The majority of juvenile NPH cases are due to deletion of the NPHP1 gene on chromosome 2q13. Genes for infantile and adolescent NPH have been localized respectively to chromosome 9q22-q31 and 3q22. A new locus, NPHP4, has been recently identified on chromosome 1p36. Two genes predisposing to dominant MCKD, MCKD1 and MCKD2, have been localized to chromosome 1q21 and 16p12. Independent confirmation of the locations of MCKD1 and MCKD2 in other MCKD families, with or without hyperuricemia and gout, has been reported. The gene for familial juvenile hyperuricemic nephropathy (FJHN), a phenotype that is very similar to MCKD, was recently mapped to 16p12, in a region overlapping with the MCKD2 locus, raising the question as to whether MCKD2 and FJHN are allelic variants of the same disease entity. The ultimate proof of the allelism between MCKD2 and FJHN will be provided by the identification of the responsible gene(s). Identification and characterization of the MCKD and FJHN genes will help to clarify the pathogenesis and classification of hereditary tubulo-interstitial nephritides.

Nefritis intersticial inmunoalérgica vs ateroembolismo de colesterol. Características diferenciales / Differential diagnosis features between acute interstitial nephritis and atheroembolic renal disease

El diagnóstico diferencial entre la nefritis intersticial inmunoalérgica (NIIA) y la enfermedad por ateroembolismo de colesterol (AE) puede ser muy difícil por presentarse a menudo ambas entidades como fracasos renales agudos con eosinofilia llamativa y lesiones cutáneas. Realizamos un estudio comparativo retrospectivo de las series de NIIA y de AE registradas en nuestro Hospital, en el período comprendido entre 1980 y diciembre del 2000. En total, se estudiaron 42 pacientes diagnosticados de NIIA y 16 pacientes diagnosticados de AE. Se analizaron los parámetros epidemiológicos, clínicos, analíticos y de evolución renal, así como la morbi-mortalidad. Se encontraron diferencias significativas en las prevalencias de sexo masculino (100% frente a 57%, p 1 g/día en un porcentaje mayor de casos de AE (44% vs 26%, p < 0,05), sin observarse diferencias en la presencia de eosinofilia (88% en la AE vs 64% en la NIIA pNS), microhematuria o leucocituria. Desde el punto de vista del pronóstico renal y la morbi-mortalidad asociada, se observa una evolución casi constante hacia la IRC terminal en el AE, así como una mortalidad elevada (69% vs 5%, p < 0,001), que contrasta con la mejor evolución de los casos con NIIA. En conclusión, la presencia de determinados datos clínicos y analíticos, en conjunto, nos permiten una orientación inicial para el diagnóstico diferencial entre ambas entidades

The commonest clinical presentation of both immunoalergic interstitial nephritis (IIN) and atheroembolic renal disease (ATD) is an acute renal failure accompanied by skin lesions and eosinophilia. As a consequence, differential diagnosis between both entities is often very difficult. We have performed a comparative retrospective study of those patients diagnosed as having IIN or ATD in our Hospital in the period 1980-2000. A total of 42 patients have been diagnosed of IIN and 16 of ATD. Demographic data, as well as clinical and laboratory parameters and outcomes of every studied patient were analysed. We found a significantly higher prevalence of male sex (100% vs 57%, p 1 g/24 h was significantly higher, but no differences between both groups in the prevalence of urinary sediment abnormalities were observed. The prevalence of absolute eosinophilia was high in both groups (88% among ATD patients, 64% among IIN patients; pNS). Prognosis of both entities was clearly different: Almost all patients with ATD died (69%) or evolved to end-stage renal failure, whereas most patients with IIN showed a recovery of renal function after withdrawal of responsible drugs and steroid treatment. In summary, the analysis of clinical and laboratory data allows an initial differential diagnosis in patients suspected as having IIN or ATD

Pyelonephritis and interstitial nephritis--clinical-pathological correlations.

AIMS: The relation between histological and clinical parameters were studied in 54 consecutive patients with acute interstitial nephritis or pyelonephritis without primary glomerular disorders, in all of whom percutaneous renal core biopsy had been performed. PATIENTS AND METHODS: Based on clinical criteria and without detailed knowledge of the appearance of the biopsy, the material was divided into 4 main groups: patients with septic and/or tubulotoxic conditions, hypersensitivity reactions (eosinophilic nephritis), ascending infections and other specified conditions. RESULTS: The overall correlation between the histological and the clinical diagnoses was good, but there were large overlaps between the histological findings in 3 of the groups, making classification of individual cases difficult. The histological and paraclinical findings were poorly correlated. Histologically, ascending infections were characterized by the presence of leukocyte casts and an increased number of neutrophilic granulocytes. CONCLUSION: The material justifies the present rough classification of the conditions mentioned above. By kidney biopsy, the interstitial conditions can be separated from glomerular and other conditions, but the biopsy offers little information about the clinical severity or the prognosis.

[The dependence of the progression of chronic glomerulonephritis on the clinical and morphological types of glomerulonephritis and on the tubulointerstitial changes]. / Zavisimost' progressirovaniia khronicheskogo glomerulonefrita ot klinicheskogo i morfologicheskogo tipov glomerulonefrita i tubulointerstitsial'nykh izmenenii.

Progression of chronic glomerulonephritis (CGN) is strongly associated with morphologic type of the disease, tubulointerstitial changes, some clinical syndromes. The aim of the study was to trace relations between the onset of chronic renal failure within 7 years since the diagnosis (fast progression of CGN--FP CGN), CGN clinical variant according to M. Ia. Ratner et al. classification (1987) and histomorphological changes in the renal biopsy. Unfavorable clinical types (active nephritic types and nephrotic-hypertensive type) proved dominating predictor of FP CGN not only because of close relationship between these type and FP CGN but also due to FP CGN occurrence in morphologically unfavorable morphological types and tubulointerstitial changes in line with concomitant unfavorable clinical types.