1. Immune mediated glomerulonephritis
2. New insight in artificial renal replacement treatments: automatic adaptive system dialysis for hemodialysis-associated hypotension and disequilibrium symptoms
3. Restless-leg sindrome in uremia
4. Substitution treatment of liver function: application of MARS (Molecular Adsorbent Recirculating System)
5. Kidney transplant: immunological aspects, cardiovascular risk factors and gene polymorphism
1. Glomerulonephritis refers to a group of relatively rare immune-mediated diseases characterized by lesions that primarily affect the renal glomeruli. If not properly treated, glomerulonephritis can progress to chronic kidney disease, leading to irreversible renal failure. According to data from US Medicare (with an average age of 75 years), approximately 1.2% of individuals are affected by these nephropathies. Certain forms of glomerular nephropathies are more prevalent and severe in specific ethnic groups, such as African-American, Hispanic, and Asian populations.
Traditionally, glomerulonephritis is classified based on typical histopathological lesions observed in renal biopsies, which remain the gold standard for assessing disease activity and chronicity. However, in recent years, advances in the understanding of pathogenetic mechanisms have led to new classification proposals. The increasing availability of immunomodulatory drugs has enabled more modern and effective treatment approaches. In addition, expanded genetic testing using next-generation sequencing has emerged as a valuable diagnostic tool for providing precise molecular diagnoses.
Renal biopsy continues to play a crucial role in diagnosis and remains the gold standard for determining disease activity and chronicity. Moreover, new urinary biomarkers of immunological activity during glomerulonephritis are now being used to monitor treatment responses.
In this context, IgA nephropathy (IgAN) is the most widespread glomerular disease globally, where complement activation plays a key role in its pathogenesis. Specifically, considering the prognostic value of serum complement levels at the time of diagnosis in IgAN patients may help assess the progression of chronic kidney disease (CKD). One study evaluated 101 patients with IgA nephropathy, stratified by baseline C3 levels into three groups (low, medium, and high), and found, after a median follow-up of 54 months, that the low C3 group had a higher incidence of chronic kidney disease. Therefore, incorporating serum C3 and C4 values into the overall assessment of IgAN patients may enhance the accuracy of predicting kidney disease progression.
2. New insight in artificial renal replacement treatments:
automatic adaptive system dialysis for hemodialysis-associated
hypotension and disequilibrium symptoms
Hemodialysis is complicated by a high incidence of intradialytic
hypotension and disequilibrium symptoms caused by hypovolemia and a
decrease in extracellular osmolarity. Automatic adaptive system
dialysis (AASD) is a dialysis system that provides automated
elaboration of dialysate and ultrafiltration profiles based on the
prescribed decrease in body weight and sodium content.
A non-controlled (single arm), multicenter, prospective,
clinical trial has been carried out on 55 patients with
intradialytic hypotension or disequilibrium syndrome in 15 dialysis
units. The patients were studied over a 1-month interval using
standard treatment (642 sessions) followed by 6 months using AASD
(2,376 sessions).
More stable intradialytic systolic and diastolic blood pressures
with lower heart rate were found using AASD compared with standard
treatment. Sessions complicated by hypotension decreased from 58.7%
± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other
disequilibrium syndrome symptoms was lower in patients receiving
AASD. This study shows the long-term clinical efficacy of AASD for
intradialytic hypotension and disequilibrium symptoms in a large
number of patients and dialysis sessions.
3. Restless-leg syndrome in uremia
Restless legs syndrome (RLS) is a sleep-related movement
disorder involving an urge to move the legs frequently in
association with unpleasant sensory symptoms. RLS can occur in 2
forms: idiopathic or secondary to other conditions including
end-stage renal disease. RLS is highly prevalent in patients on
maintenance dialysis and ESRD patients with sleep disorders which
are independently linked to a higher mortality rate. We evaluated
the impact of chronic inflammation on RLS in dialysis patients. 100
patients in dialysis for at least 3 months were included in this
study. A specific questionnaire based on the criteria of the
International Restless Legs Syndrome Study Group (IRLSSG) was used
to asses the prevalence of RLS. Gender, age on starting dialysis,
time on dialysis, BMI, blood pressure, tobacco use, comorbidities
and drugs were recorded. The basal values of hemoglobin,
hematocrit, CRP, PTH, calcium, phosphorus, albumin, alkaline
phosphatase, total-, HDL- and LDL-cholesterol, triglycerides, uric
acid, fibrinogen, erythrocyte sedimentation rate (ESR), iron,
ferritin, transferrin, electrolytes were assayed in each patient.
RLS was observed in 31/100 (31%). Univariate analysis revealed
positive correlations between RLS and female gender (p=0.048),
polyneuropathy (p=0.031), fibrinogen (p=0.004), ESR (p=0.004), CRP
(p=0.025), white blood cells (WBC) (p=0.023), albumin (p=0.018).
After adjustment for age, dialysis vintage, gender and Charlson
score, multivariate analysis showed that CRP (p=0.041), fibrinogen
(p=0.002), ESR (p=0.005), albumin (p=0.026) and WBC (p=0.022) were
significant independent predictors for RLS. This study revealed a
higher prevalence of RLS in dialysis patients, thus suggesting a
role in the pathogenesis of RSL of chronic inflammation, besides
the well-known associations with atherosclerosis, malnutrition,
longer hospitalizations and cardiovascular mortality (La Manna G,
et al. Restless legs syndrome enhances cardiovascular risk and
mortality in patients with end-stage kidney disease undergoing
long-term haemodialysis treatment. Nephrol Dial Transplant. 2010
Nov 5).
4. Substitution treatment of liver function: Application of
MARS (Molecular Adsorbent Recirculating System)
An important research line is the application of Molecular
Adsorbents Recirculating regards the System (MARS) in the treatment
of liver failure. The principle of this method is based on the use
of an extracorporeal circuit similar to that of hemodialysis,
combined with an albumin circuit. This allows to remove from the
blood not only free toxins, but also the albumin-bound toxins (bile
acids, aromatic compounds, bilirubin, mercaptans, ammonia, lactic
acid). This study was focused on the effectiveness of treatment in
22 patients with acute liver failure and acute on chronic liver
failure, with the aim to assess not only of the patients' clinical
situation, but also the efficiency of the MARS circuit in the
removal of bilirubin, ammonia, bile acids and urea, the indices of
biocompatibility, the acid-base balance and electrolyte. We have
also measured plasma levels of inflammatory cytokines (IL-1beta,
IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, TNF-alpha,
IFN-gamma) and major hepatic growth factors (EGF and HFG) pre-and
post-MARS treatment in order to analyze the effects on inflammation
and liver regeneration.
5. Kidney transplant: immunological aspects, cardiovascular
risk factors and gene polymorphism
Cardiovascular disease (CVD) represents the main cause of morbidity
and mortality after renal transplantation. A pathogenetic link
between inflammation, atherosclerosis and CVD have been
demonstrated. For this reason, genetic factors regulating cytokine
production and the balance between pro- and anti- inflammatory
molecules could have a deep influence on CVD risk. In the view of
the modern paradigm of atherosclerosis as an inflammatory disease,
the present study was undertaken to investigate the impact of
inflammatory cytokine polymorphisms on post-renal transplant CVD.
To evaluate the association between cytokine polymorphisms and CVD,
a case-control study was carried out on 798 renal allograft
recipients transplanted between 1997 and 2008, 196 of them with CVD
(CVD group) and 602 controls free of cardiovascular complications
(no-CVD group). TNF-α/G-308A, TGF-β1/L10P, TGF-β1/R25P,
IL-10/G-1082A, IL-10/C-819T, IL-10/C-592A, IL-6/G-174C,
IFN-γ/T+874A, IL-8/T-251A and VEGF/C+936T polymorphisms were
genotyped using PCR-SSP and RFLP. The patients in CVD and no-CVD
group differed significantly in IL-10 and TNF-α genotype frequency.
Using multivariate analyses to test the association with CVD, the
high producer genotype of the pro-inflammatory cytokine TNF-α was
significantly associated with a 4.41-fold increased cardiovascular
risk. Conversely, the carriage of high producer genotype of the
anti-inflammatory cytokine IL-10 resulted protective against
post-transplant CVD, with an adjusted OR of 0.2 (0.02-0.29). This
work seems to indicate that gene polymorphisms involved in
inflammatory response might represent cardiovascular risk markers
in renal allograft recipients and suggests a prognostic value of
TNF-α and IL-10 genotypes. Further studies are necessary to
evaluate if patients with a CVD "predisposing" genotype should be
treated more aggressively (La Manna G, Cappuccilli ML, Capelli I,
Baraldi O, Cuna V, Battaglino G, Feliciangeli G, Dormi A, Scolari
MP, Stefoni S. The impact of apoptosis and inflammation gene
polymorphisms on transplanted kidney function. Ann Transplant. 2013
Jun 4;18:256-64.)
