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Medicina
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Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment
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Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Urology & Nephrology".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 26645

Special Issue Editor

Dr. Giovanni Conti

E-Mail Website
Guest Editor
Pediatric Nephrology Unit, AOU Policlinic “G Martino”, University of Messina, 98125 Messina, Italy
Interests: pediatric nephrology; pediatric rheumatology; clinical nephrology; glomerulonephritis; nephrotic syndrome; rare diseases; autoimmune diseases; autoinflammatory diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues

Glomerulonephritis, one of the leading causes of end-stage renal disease, is a group of rare diseases with different presentations, clinical courses, and outcomes. The main causes of chronic kidney disease are hypertension and diabetes, which mainly affect adulthood. However, there are several chronic glomerulonephritis types or idiopathic or secondary to autoimmune diseases that instead begin in adolescent or juvenile age. Kidney biopsy remains the cornerstone for the evaluation of these glomerular diseases. The incidence depends on the type of glomerulonephritis but is usually underestimated (asymptomatic variants, spontaneous remission, infeasible renal biopsy). A descriptive glomerulonephritis classification, based largely on histological patterns, is increasingly being replaced on the basis of new pathogenic insights. In recent years, clinical and laboratory research has made significant contributions to the understanding of the pathogenesis of glomerulonephritis that is however still uncertain and not completely understood. These glomerular diseases are one of the few categories of kidney disease that are treatable, but the management remains a challenge for nephrologists. Current treatment is based on the use of corticosteroids and immunosuppressive drugs. These drugs, which have improved the course of these chronic glomerulonephritis diseases, are however toxic and have many side effects. Recent pathogenetic knowledge has determined the development of a new therapy, especially biological drugs, with excellent efficacy and few side effects.

This Special Issue will deal with several aspects of prognostic risk factors, pathogenesis and treatment of glomerulonephritis, as specified below.

Dr. Giovanni Conti
Guest Editor

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Keywords

  • Glomerulonephritis
  • Nephrotic syndrome
  • Autoimmune diseases
  • Autoinflammatory diseases
  • Amiloidosis
  • Immunosuppressive therapy
  • Biologic drugs

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Published Papers (4 papers)

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Review

11 pages, 334 KiB  
Review
Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever
by Rossella Siligato, Guido Gembillo, Vincenzo Calabrese, Giovanni Conti and Domenico Santoro
Medicina 2021, 57(10), 1049; https://doi.org/10.3390/medicina57101049 - 1 Oct 2021
Cited by 27 | Viewed by 5105
Abstract
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically [...] Read more.
Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis. Full article
(This article belongs to the Special Issue Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment)
22 pages, 653 KiB  
Review
The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies
by Michela Amatruda, Guido Gembillo, Alfio Edoardo Giuffrida, Domenico Santoro and Giovanni Conti
Medicina 2021, 57(9), 868; https://doi.org/10.3390/medicina57090868 - 25 Aug 2021
Cited by 25 | Viewed by 6525
Abstract
Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset [...] Read more.
Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression. Full article
(This article belongs to the Special Issue Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment)
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9 pages, 830 KiB  
Review
Renal Morphology in Coronavirus Disease: A Literature Review
by Patrick de Oliveira, Kaile Cunha, Precil Neves, Monique Muniz, Giuseppe Gatto, Natalino Salgado Filho, Felipe Guedes and Gyl Silva
Medicina 2021, 57(3), 258; https://doi.org/10.3390/medicina57030258 - 11 Mar 2021
Cited by 14 | Viewed by 3365
Abstract
Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and [...] Read more.
Renal biopsy is useful to better understand the histological pattern of a lesion (glomerular, tubulointerstitial, and vascular) and the pathogenesis that leads to kidney failure. The potential impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the kidneys is still undetermined, and a variety of lesions are seen in the kidney tissue of coronavirus disease patients. This review is based on the morphological findings of patients described in case reports and a series of published cases. A search was conducted on MEDLINE and PubMed of case reports and case series of lesions in the presence of non-critical infection by SARS-CoV-2 published until 15/09/2020. We highlight the potential of the virus directly influencing the damage or the innate and adaptive immune response activating cytokine and procoagulant cascades, in addition to the genetic component triggering glomerular diseases, mainly collapsing focal segmental glomerulosclerosis, tubulointerstitial, and even vascular diseases. Kidney lesions caused by SARS-CoV-2 are frequent and have an impact on morbidity and mortality; thus, studies are needed to assess the morphological kidney changes and their mechanisms and may help define their spectrum and immediate or long-term impact. Full article
(This article belongs to the Special Issue Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment)
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Figure 1

15 pages, 405 KiB  
Review
Vitamin D and Glomerulonephritis
by Guido Gembillo, Rossella Siligato, Michela Amatruda, Giovanni Conti and Domenico Santoro
Medicina 2021, 57(2), 186; https://doi.org/10.3390/medicina57020186 - 22 Feb 2021
Cited by 30 | Viewed by 8450
Abstract
Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeostasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease [...] Read more.
Vitamin D presents a plethora of different functions that go beyond its role in skeletal homeostasis. It is an efficient endocrine regulator of the Renin–Angiotensin–Aldosterone System (RAAS) and erythropoiesis, exerts immunomodulatory effects, reduces the cardiovascular events and all-cause mortality. In Chronic Kidney Disease (CKD) patients, Vitamin D function is impaired; the renal hydrolyzation of its inactive form by the action of 1α-hydroxylase declines at the same pace of reduced nephron mass. Moreover, Vitamin D major carrier, the D-binding protein (DBP), is less represented due to Nephrotic Syndrome (NS), proteinuria, and the alteration of the cubilin–megalin–amnionless receptor complex in the renal proximal tubule. In Glomerulonephritis (GN), Vitamin D supplementation demonstrated to significantly reduce proteinuria and to slow kidney disease progression. It also has potent antiproliferative and immunomodulating functions, contributing to the inhibitions of kidney inflammation. Vitamin D preserves the structural integrity of the slit diaphragm guaranteeing protective effects on podocytes. Activated Vitamin D has been demonstrated to potentiate the antiproteinuric effect of RAAS inhibitors in IgA nephropathy and Lupus Nephritis, enforcing its role in the treatment of glomerulonephritis: calcitriol treatment, through Vitamin D receptor (VDR) action, can regulate the heparanase promoter activity and modulate the urokinase receptor (uPAR), guaranteeing podocyte preservation. It also controls the podocyte distribution by modulating mRNA synthesis and protein expression of nephrin and podocin. Maxalcalcitol is another promising alternative: it has about 1/600 affinity to vitamin D binding protein (DBP), compared to Calcitriol, overcoming the risk of hypercalcemia, hyperphosphatemia and calcifications, and it circulates principally in unbound form with easier availability for target tissues. Doxercalciferol, as well as paricalcitol, showed a lower incidence of hypercalcemia and hypercalciuria than Calcitriol. Paricalcitol demonstrated a significant role in suppressing RAAS genes expression: it significantly decreases angiotensinogen, renin, renin receptors, and vascular endothelial growth factor (VEGF) mRNA levels, thus reducing proteinuria and renal damage. The purpose of this article is to establish the Vitamin D role on immunomodulation, inflammatory and autoimmune processes in GN. Full article
(This article belongs to the Special Issue Glomerulonephritis: Pathogenesis, Risk Factors, and Treatment)
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