Hydralazine-induced ANCA vasculitis with pulmonary renal syndrome: a rare clinical presentation

Hydralazine is a commonly used drug for treatment of hypertension and is known to cause drug-induced lupus erythematosus. It has rarely been reported to cause anti neutrophil cytoplasmic antibody positive vasculitis, a life-threatening complication. Presentation could be extremely variable delaying diagnosis. Although drug-induced vasculitis has been infrequently associated with rapidly progressing glomerulonephritis, pulmonary involvement presenting as pulmonary renal syndrome is extremely rare. We report a case of hydralazine-induced vasculitis presenting as pulmonary renal syndrome with fatal outcome even after aggressive treatment. Numerous antibodies are associated with hydralazine including anti myeloperoxidase antibody, anti-nuclear antibody, anti-histone antibody, and anti-elastase antibody. Additionally, we also report the presence of anti-phospholipid antibodies specific to anti-cardiolipin, anti-beta2 glycoprotein, and anti-phosphatid that have not been previously reported. We conclude that early diagnosis and prompt discontinuation of the drug is necessary for the treatment of hydralazine-induced anti neutrophil cytoplasmic antibody vasculitis.     

Discrimination between postinfectious IgA-dominant glomerulonephritis and idiopathic IgA nephropathy

Background: A unique form of postinfectious glomerulonephritis (PIGN) with IgA-dominant deposition mimicking IgA nephropathy has been increasingly reported. Methods: We compared the clinical and histological features of 12 patients with postinfectious IgA-dominant glomerulonephritis to 134 patients with idiopathic IgA nephropathy. Results: In addition to hypocomplementemia and subepithelial hump-shaped deposits characteristic of PIGN, patients with postinfectious IgA-dominant glomerulonephritis had older age (62.3 ± 16.9 vs. 37.9 ± 16.3 years; p < 0.001) and more frequently presented with acute renal failure (83.3% vs. 10.4%; p < 0.001) than patients with idiopathic IgA nephropathy. Moreover, glomerular changes including endocapillary proliferation, neutrophil infiltration, and capillary loops deposits by immunofluorescence were more commonly present in postinfectious IgA-dominant glomerulonephritis group (p < 0.001). Conclusions: PIGN could be characterized by glomerular IgA-dominant deposition resembling idiopathic IgA nephropathy. It is essential to differentiate postinfectious IgA-dominant glomerulonephritis from idiopathic IgA nephropathy because of the different treatments and prognosis of the two diseases.     

Glomerulonephritis associated with acute pneumococcal pneumonia: a case report

Streptococcus pyogenes is the most common cause of post-infectious glomerulonephritis. There have been isolated case reports of nephritis following infections with Streptococcus pneumoniae. We report here the case of a 6-year-old white female who presented with blood culture-confirmed pneumococcal pneumonia associated with glomerulonephritis. Her acute renal failure improved over several days, and renal function was normal by 8 weeks post-hospitalization. This case serves to reinforce the concept that other organisms besides Streptococcus pyogenes can trigger a similar post-infectious glomerulonephritis and should be considered in the differential diagnosis of any child who presents with acute glomerulonephritis and respiratory findings. Additionally, pneumococcus group 7 may be a nephritogenic strain and requires further investigation.     

Acute Postinfectious Crescentic Glomerulonephritis: Clinicopathologic Presentation and Risk Factors

Background: Glomerular crescent formation is a feature of the most severe forms of human glomerulonephritis. The postinfectious form of rapidly progressive glomerulonephritis with crescents is a form of immune complex glomerulonephritis which seem to have a better prognosis. A relatively poorer prognosis for crescentic postinfectious glomerulonephritis in South Africa has been reported. In the present study, we have tried to determine the mode of presentation, and the prognostic factors for renal and patient outcome for cases with postinfectious crescentic glomerulonephritis (CGN). Methods:Between 1990 and 2000 a total number of 128 patients with CGN were managed at our center, among them 23 cases were diagnosed as postinfectious CGN. They were followed-up for a mean period of 40.1 ± 28.9 months. Among them 12 were males and 11 were females. The median age was 12.35 years (range 4–55 years). The median serum creatinine at presentation was 7.24 mg/dl (range 1.3–14.5 mg/dl). We studied the clinical, laboratory and histopathological data ^.of our cases and their impact on the renal and patient outcome. Results:By univariate study the risk factors for renal dysfunction were the age, hypertension, and nephrotic range proteinuria during the follow-up period. By multivariate analysis only the, hypertension, and presence of nephrotic range proteinuria during the follow-up period were the significant risk factors. The risk factors that significantly affected patient mortality were hypertension and serum creatinine at last follow-up. Conclusion: postinfectious CGN is a severe form of glomerulonephritis that usually presents with rapidly progressive renal failure. The persistence of hypertension and nephrotic range proteinuria during the follow-up are major bad prognostic predictors for renal dysfunction.     

Néphropathie associée à une vascularite urticarienne hypocomplémentémique : présentation d’un cas clinique et revue de la littérature

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot–Sjögren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.     

Recurrent acute postinfectious glomerulonephritis

Recurrent acute postinfectious glomerulonephritis is infrequent in childhood and exceptional in adults. The factors that determine recurrence are poorly understood. Selective IgA deficiency is characterized by an increased incidence of gastrointestinal and respiratory infections. The case of a 33-year-old man with a history of repetitive sinopulmonary infections and diagnosed with selective IgA deficiency is described. He suffered 2 episodes of postinfectious glomerulonephritis within a 15-year period. Selective IgA deficiency may have predisposed to the development of recurrent postinfectious glomerulonephritis     

Rapidly progressive renal failure in type 2 diabetes in the tropical environment: a clinico-pathological study

BACKGROUND: Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. METHODS: Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. RESULTS: A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine >4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. CONCLUSIONS: About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

Renal involvement in leprosy: report of progression from diffuse proliferative to crescentic glomerulonephritis

Renal involvement in leprosy has been reported rarely in the literature. Acute kidney injury in patients with leprosy is uncommon and may occur due to acute tubular necrosis, drug-induced interstitial nephritis and rarely crescentic glomerulonephritis. The latter with histologic confirmation of the diagnosis has been reported in very few cases of leprosy. A 25-year-old male, on therapy for multibacillary leprosy, was found to have deranged renal functions on evaluation for a history of nausea, vomiting, swelling and episode of haematuria. Kidney biopsy was performed twice over a period of 2 weeks, showing progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis, pauci-immune in nature. The patient was treated aggressively with intravenous steroids, following which his renal functions stabilized. Crescentic glomerulonephritis, an extremely rare phenomenon in leprosy, should be considered in these patients presenting with features of acute kidney injury. Timely performed renal biopsy assists in accurate diagnosis and appropriate management of the patient, hence preserving renal parenchyma. Rapid progression from diffuse proliferative glomerulonephritis to crescentic glomerulonephritis in a patient with leprosy is described herein for the first time in the literature.     

Pneumococcal capsular antigen detection and pneumococcal serology in patients with community acquired pneumonia.

BACKGROUND: Methods to determine the microbial cause of community acquired pneumonia include detection of pneumococcal antigen and measurement of pneumococcal capsular antibody response. Their usefulness compared with conventional microbiological techniques was investigated in patients with pneumonia, some of whom had been treated with antibiotics. METHODS: Pneumococcal capsular antigen was detected by latex agglutination in sputum and the results compared prospectively with results of conventional microbiological techniques in 90 patients with community acquired pneumonia. Serum, urine, and pleural fluid samples were also tested for antigen. Serum pneumococcal capsular antibody titres were measured. RESULTS: A diagnosis was established by conventional microbiological techniques in 53 patients, 30 of whom had pneumococcal pneumonia. The sensitivity of antigen detection in first day sputum specimens (n = 18) in those with pneumococcal pneumonia was 94%; antigen was present in 23 of the 27 patients who produced representative sputum on admission and during follow up. The specificity of antigen detection in sputum in patients with non-pneumococcal pneumonia and lung infarction was 87%. Antigen was present in 12 of 25 patients with pneumonia of unknown aetiology who produced representative sputum. Antigen was rarely detected in serum and urine, but was present in pleural fluid in three of four patients with pneumococcal pneumonia and in all four patients with pneumonia of unknown aetiology. Pneumococcal antigen remained detectable in patients treated with antibiotics. Pneumococcal capsular antibody detection was as specific (85%) as antigen detection, but had a lower sensitivity (50%). CONCLUSION: Pneumococcal antigen detection in sputum or pleural fluid is of value in making a rapid diagnosis and provides an additional diagnostic result in patients with pneumococcal pneumonia, especially those receiving antibiotic treatment.     

Austrian triad with sinus of Valsalva aneurysm and rupture

An interesting case of a young patient presenting with Austrian's Triad: pneumococcal pneumonia, pneumococcal meningitis, and pneumococcal endocarditis. On echocardiogram the patient was noted to have a noncoronary sinus of Valsalva aneurysm and vegetations on the aortic cusps resulting in disruption of valvular integrity and severe aortic insufficiency. Color Doppler also revealed rupture of the aneurysm into the right atrium. The patient was taken to surgery where the noncoronary cusp was noted to be completely replaced with vegetative lesions. The aortic valve was replaced with a No. 21 Carpentier-Edwards bioprosthetic valve (Edwards Lifesciences, Irvine, CA), and the noncoronary sinus of Valsalva was repaired with concomitant closure of the fistula using glutaraldehyde autologous pericardium.     

Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis in a patient receiving treatment with etanercept for severe rheumatoid arthritis

Etanercept is a tumor necrosis factor inhibitor used in the treatment of rheumatoid arthritis and, increasingly, in a range of other diseases. We report a case of necrotizing crescentic glomerulonephritis, associated with a positive antineutrophil cytoplasmic antibody, causing acute renal failure in a woman receiving treatment with etanercept for severe rheumatoid arthritis. Our patient was treated with steroids and cyclophosphamide following withdrawal of etanercept, with a good clinical response. Although reports of vasculitis in patients receiving treatment with etanercept are rare, this drug has been shown to up-regulate some aspects of immune function, and the possibility that this agent may precipitate or exacerbate vasculitis in some individuals has to be considered.     

Increased risk of pneumococcal infections in cardiac transplant recipients

We observed 5 episodes of pneumococcal infection among 129 cardiac transplant patients between March 1985 and December 1987, giving an estimated incidence of 36 cases per 1000 patient-years. Infections occurred a mean of 58 days after transplantation and included bacteremia with empyema, bacteremia alone, and pneumonia. All patients recovered from their infections. There was no correlation between infection and age, sex, immunosuppression, or rejection episodes. We also measured antibody levels to 12 pneumococcal antigens in 6 unvaccinated, uninfected patients before and after cardiac transplantation, to see if baseline antibody levels decreased. Protective levels of antibody were defined as greater than or equal to 300 ng of anticapsular antibody nitrogen per milliliter serum. Before transplantation patients had protective antibody levels to a mean of 8.7 +/- 1.2 pneumococcal serotypes; after transplantation, the number of presumably protective antibody levels decreased to 6.5 +/- 1.4 (P = 0.021). One of these patients subsequently developed pneumococcal pneumonia. Cardiac transplant patients are at increased risk of pneumococcal infections. Vaccinating transplant candidates prior to transplantation may provide protection after transplantation.     

Rapidly Progressive Renal Failure in Type 2 Diabetes in the Tropical Environment: A Clinico-Pathological Study

Background. Rapid decline of renal function in a diabetic suggests the presence of a nondiabetic kidney disease (NDKD). We designed a prospective study to evaluate the factors associated with a rapid decline in renal function in patients with type 2 diabetes. Methods. Over a 2 and a half year period, all patients with type 2 diabetes who presented with documented doubling of serum creatinine in less than 4 weeks or recently diagnosed advanced renal failure were identified. Patients with prerenal causes, urinary tract obstruction, or systemic disease causing renal failure were not included. Renal histology was studied in all cases. Results. A total of 26 patients satisfied the inclusion criteria. Over 75% had serum creatinine > 4 mg/dL at presentation and 62% were dialysis dependent. Renal histology showed mixed lesions of diabetic nephropathy (DN) and NDKD in 11 cases, only DN in nine, and pure NDKD in six. Diffuse proliferative glomerulonephritis (DPGN) was the commonest NDKD (27% cases), all on a background of DN. History of preceding cutaneous or pharyngeal infection was available in five cases. The proportion of postinfectious glomerulonephritis in diabetics with rapidly progressive renal failure was over six times that of the nondiabetic adult RPRF population during the study period. Four patients had acute interstitial nephritis and three showed crescentic glomerulonephritis. Other lesions included amyloidosis, atheroembolic disease, and renal papillary necrosis (one each). The frequency of microscopic hematuria and retinopathy was similar in those with pure DN and NDKD. Four out of seven cases with DPGN showed partial recovery whereas the other three remained unchanged. Conclusions. About two-thirds of patients with type 2 diabetes presenting with rapid decline of renal function in a tropical environment show NDKD. The high incidence of postinfectious glomerulonephritis in this group is possibly related to the high prevalence of skin and soft tissue infections; and could contribute to progressive kidney disease.     

Efficacy of pneumococcal immunization in patients with renal disease--what is the data?

BACKGROUND/AIMS: There is an increased incidence of invasive pneumococcal disease in patients with renal allografts, chronic renal insufficiency (CRI), or nephrotic syndrome (NS). Routine pneumococcal immunization (PI) has been recommended for these patients, but the efficacy of PI in this population is not well established. METHODS: A review was done of studies that reported the immunologic response, efficacy, or safety of PI in patients with renal allografts, CRI, or NS. RESULTS: On review of 26 published studies of PI in this population, all studies demonstrated a serologic response by the majority of patients to at least some pneumococcal serotypes. Use of steroids did not alter this response. In the studies with a greater than 6-month follow-up, declining antibody titers were consistently reported, and this decline was usually more rapid than in healthy controls. However, because the studies of the efficacy of PI in this population involve small numbers of patients and are not controlled, the significance of this decline in titers is not known. The incidence of serious adverse reactions to PI is very low. CONCLUSION: Pending more data, patients with renal transplants, CRI, or NS should continue to be offered PI.     

Association of a novel complement factor H mutation with severe crescentic and necrotizing glomerulonephritis

Severe crescentic and necrotizing glomerulonephritis typically is associated with anti-glomerular basement membrane or antineutrophil cytoplasmic antibodies. In this report, we describe a 23-year-old man with severe crescentic and necrotizing glomerulonephritis. Both anti-glomerular basement membrane and antineutrophil cytoplasmic antibody titers were negative. Kidney biopsy showed bright C3 staining in the mesangium and along capillary walls and no staining for immunoglobulins. Electron microscopy showed waxy deposits (many mesangial; few intramembranous or subendothelial), prompting evaluation of the alternative pathway of complement. Alternative pathway evaluation showed a novel mutation in short consensus repeat (SCR) 19 of complement factor H. In addition, the patient carried complement factor H and C3 risk alleles. Prompt treatment with intravenous steroids followed by oral steroids resulted in symptom alleviation and improved kidney function. This case shows what is to our knowledge a unique and previously unpublished cause of severe crescentic and necrotizing glomerulonephritis. Furthermore, the case demonstrates an expanding spectrum of complement-mediated glomerulonephritis and shows that crescentic and necrotizing glomerulonephritis with solely complement deposits should be evaluated for abnormalities in the alternative pathway of complement.     

Acute post-streptococcal glomerulonephritis in a renal allograft

We report a 12-year-old male with acute post-streptococcal glomerulonephritis (APSGN) occurring 1 year after a cadaveric renal transplant. Although recurrent and de novo renal transplant glomerulonephritides have been well described in large series of adult and pediatric renal transplant recipients, post-infectious glomerulonephritis has been rarely reported, and APSGN has never been reported in either adult or pediatric transplant series. We speculate on the reasons for the lack of occurrence of APSGN in renal transplant recipients.     

Persistence of protective pneumococcal antibody following vaccination in patients with the nephrotic syndrome

We have determined the level of persisting pneumococcal antibody in a group of nephrotic children vaccinated by us 5 years ago. Of the 19 vaccinated children, 2 have died and 1 has moved away. Sera from the remaining 16 patients were examined by radioimmunoassay to determine the antibody response to 11 of the 14 types contained in the polyvalent pneumococcal vaccine. The lowest protective level of geometric mean titre (GMT) of antibody in our laboratory is 300 ng antibody nitrogen per millilitre. 56% (9/16) of the patients showed adequate GMT 5 years after vaccination. All 9 patients had minimal change nephrotic syndrome. 44% (7/16) of the children had a GMT less than 300 ng antibody nitrogen per millilitre. 3 of these patients had focal sclerosis, 3 had membranoproliferative glomerulonephritis, and 1 patient had IgM nephropathy. Of these 7 patients, 1 with the lowest GMT (23 ng antibody nitrogen per millilitre) developed pneumococcal peritonitis. During this same period, in 20 other unvaccinated nephrotic patients followed continuously from 1976 to 1981, 7 cases of pneumococcal peritonitis occurred (p less than 0.05). Additionally, 1 unvaccinated child died of pneumococcal sepsis. Our study indicates that patients with minimal change nephrotic syndrome continue to maintain adequate amounts of antibody, but those with disease other than minimal change nephrotic syndrome are unable to maintain an adequate level of antibody.     

Waldenstrom's macroglobulinemia presenting as Goodpasture's syndrome

We report a case of Waldenstrom's macroglobulinemia (WM) presenting as classic Goodpasture's syndrome. Thrombocytopenia, an additional autoimmune phenomenon, further complicated the clinical course. Renal disease is well recognized in Waldenstrom's macroglobulinemia and other B-cell dyscrasias. Similarly, a wide spectrum of autoimmune-mediated conditions has been reported in association with paraproteinemia. However, rapidly progressive glomerulonephritis in association with antiglomerular basement membrane antibodies has never been reported as either an autoimmune or a renal manifestation of WM. This article reviews the current understanding of renal pathology and autoimmune phenomenon associated with WM.     

Membranoproliferative glomerulonephritis associated with small cell lung carcinoma

An association between nephropathy and malignant solid tumours or with lymphoproliferative disorders was repeatedly reported. This association is mainly manifested by a nephrotic syndrome. In Lee's study [14], 11% of the adult nephrotics whom they had seen over a ten-year period developed a carcinoma. Membranous glomerulonephritis (MGN) is the most common glomerular disease associated with malignant solid tumour; the association of membranoproliferative glomerulonephritis (MPGN) with solid tumour is still uncommon. Although lung carcinoma is relatively common, the incidence of glomerular involvement with this tumour is quite rare. To date, only a few cases of lung cancer associated with nephrotic syndrome or glomerulonephritis have been reported by various authors. MGN is the most common glomerular lesion associated with these cases; however, MPGN has not been reported to be associated with lung cancer before. We report on a 45-year old man with nephrotic syndrome due to MPGN which in this case seemed to be a component of the paraneoplastic syndrome.     

IgA nephropathy: acute renal failure, acute tubular necrosis, and features of postinfectious acute glomerulonephritis.

From 1976 to 1987 on our Nephrological Unit, 57 patients with IgA nephropathy (IgAN) proven by renal biopsies were found. Three of those presented with acute tubular necrosis (ATN) and glomerulitis, without extrarenal predisposing cause in two; and showed, as prominent manifestation, a severe acute renal failure syndrome (ARFS), needing dialytic treatment. All three had hematuria, which was macroscopic in two and microscopic in one. Thus the prevalence of the association of glomerulitis and ATN was about 5.2%. There was complete recovery of renal functions in all three patients, but the usual symptomatology of IgAN. Two patients presented polymorphonuclear neutrophils infiltration of glomerular capillaries and in one of them, electron-dense deposits on the epithelial side of glomerular basement membrane ("humps") were observed, as well as those identified in the mesangial area. The glomerular polymorphonuclear neutrophils infiltration and endothelial cells proliferation (cases 1 and 3), the presence of "humps" (case 1), high antistreptolysin O (ASO) titers (cases 1 and 2), and low serum complement levels (case 1), suggest the possibility that antigens able to cause postinfectious glomerulonephritis (streptococcal or not) could induce in some individuals, by another immunopathogenetic route, mixed histopathological and clinical features of IgAN and postinfectious glomerulonephritis.