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\begin{document}

\title{A rare renal involvement in a patient with axial Spondyloarthritis:
don't miss focal segmental glomerulosclerosis and hyalinosis}



\author[1]{Tbini Houssem }%
\author[1]{Soumaya Boussaid}%
\author[2]{ikram mami}%
\author[3]{Sonia Rekik}%
\author[1]{Lilia Ben Fatma}%
\author[4]{Samia Jemmali}%
\author[2]{hela jebali}%
\author[1]{hela Sahli}%
\author[2]{lamia rais}%
\author[2]{karim zouaghi}%
\author[3]{mohamed elleuch}%
\affil[1]{Hôpital La Rabta}%
\affil[2]{Department of Nephrology La Rabta Hospital, Tunis – Tunisia. }%
\affil[3]{Hopital La Rabta}%
\affil[4]{Universite de Tunis El Manar Faculte de Medecine de Tunis}%


\vspace{-1em}



  
  \date{May 15, 2024}


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\selectlanguage{english}
\begin{abstract}
Renal involvement in spondyloarthritis is dominated by amyloidosis, IgA
nephropathy and urolithiasis. Other nephropathies are rare . A patient
followed for SpA consults with edema , hydrocele and a pleural effusion.
A FSGS was confirmed by renal biopsy and the etiological investigation
has ruled out the causes of secondary FSGS.%
\end{abstract}%



\sloppy


\textbf{A rare renal involvement in a patient with axial
Spondyloarthritis: don't miss focal segmental glomerulosclerosis and
hyalinosis}

\textbf{Soumaya Boussaid\textsuperscript{1,3}, Tbini
Houssem\textsuperscript{1,3}, Ikram Mami\textsuperscript{2,3}, Sonia
Rekik\textsuperscript{1,3}, Lilia Ben Fatma\textsuperscript{2,3}, Samia
Jammali\textsuperscript{1,3}, Hela Jbali\textsuperscript{2,3}, Hela
Sahli\textsuperscript{1,3}, Lamia Rais\textsuperscript{2,3}, Mohamed
Karim Zouaghi\textsuperscript{2,3}, Mohamed
Elleuch\textsuperscript{1,3}}

\textsuperscript{\textbf{1}}\textbf{Rheumatology Department, Rabta
Hospital, Tunis, Tunisia}

\textsuperscript{\textbf{2}}\textbf{Nephrology,~Dialysis and Renal
Transplantation Department, Rabta Hospital, Tunis, Tunisia}

\textsuperscript{\textbf{3}}\textbf{Faculty of Medicine of Tunis,
University Tunis el Manar, Tunis, Tunisia}\emph{}

\textbf{Key Clinical Message:}

Renal involvement in SpA should not be missed, screening these patients
during follow-up allows early detection of any impairment and helps
guide early nephroprotection and treatment measures. AA amyloidosis, IgA
nephropathy and urolithiasis are the most reported, however, other rare
involvement can be described.\textbf{}

\textbf{Abstract}

Renal involvement in spondyloarthritis is rare and it is dominated by AA
amyloidosis, IgA nephropathy and urolithiasis. Other nephropathies are
rare and are limited to few case reports. \textbf{Description of the
case:} we report a case of a patient followed for axial SpA who
developed a focal segmental glomerulosclerosis and hyalinosis. Indeed,
he consults after being lost to follow-up for 3 years with edema of the
2 lower limbs associated with a hydrocele and a bilateral pleural
effusion of low abundance. A FSGS was confirmed by renal biopsy and the
etiological investigation has ruled out the causes of secondary
FSGS.\textbf{Conclusion:} Although renal involvement is rare in SpA,
screening those patients in order to early detect any renal impairment
is important during disease monitoring.

\textbf{Key words:}

Spondyloarthritis; Renal involvement; Focal segmental glomerulosclerosis
and hyalinosis

\textbf{Introduction:}

Spondyloarthritis (SpA) is a chronic inflammatory rheumatism most
commonly affecting young men. It is characterized by pelvic-spinal
involvement which may be isolated or associated with peripheral joint
and/or enthesitic involvement and by association with the human
leukocyte antigen B27 (HLA-B27) haplotype (1).

Among the extra-articular manifestations of SpA, renal involvement is
rare and mostly severe . AA amyloidosis, IgA nephropathy and
urolithiasis are the most common causes. However, other nephropathies
could be seen in SpA; they are rare and limited to case reports (2,3).
Thus, we report the case of a focal segmental glomerulosclerosis and
hyalinosis (FSGS) in a patient with axial SpA.

\textbf{Case:}

A 49-year-old man with a history of retrobulbar optic neuritis was
diagnosed with axial SpA since 2017. The diagnosis was made according to
ASAS 2009 criteria (inflammatory chronic back pain over one year,
positive C-Reactive-Protein (CRP) at 164mg/l and bilateral sacroiliitis
on X ray (grade II)) (4). There was no extra-articular manifestation at
the time of the disease diagnosis. He was treated with Non-Steroidal
Anti-Inflammatory Drugs NSAIDs (diclofenac and indomethacin) for a
period of two months. This treatment was quickly stopped upon the
discovery of proteinuria at 0.3 g/24h. The patient was put on
corticosteroid therapy (10 mg of Prednisone) and we decided to put him
on biotherapy (Adalimumab).

The patient was lost to follow-up from 2017 to 2020. He consulted in
December 2020 with edema of lower limbs, a hydrocele, and a bilateral
pleural effusion of low abundance. His blood pressure was high (180-200
mmHg systolic). On osteoarticular examination, there were back stiffness
and limitation in hips mobility. Moreover, there were no other articular
involvement or abnormalities in the general examination.

Laboratory investigations showed: CRP at 51mg/l, normal level of urea
and creatinine, the 24-hour urine protein was at 5.9 g/24h, the
proteinemia was at 46g/l and the albuminemia was at 14.4g/l and there
was not h\selectlanguage{ngerman}ématuria. In front of those clinical and biological data; we
retained the diagnosis of impure nephrotic syndrome with arterial
hypertension. Regarding SpA activity, the Bath Ankylosing Spondylitis
Disease Activity score (BASDAI) was at 6.3, the Ankylosing Spondylitis
Disease Activity Score (ASDAS CRP) was at 4.95. By questioning the
patient, he affirmed that he self-administrated paracetamol and NSAIDs
occasionally in case of pain.

To explore the impure nephrotic syndrome, a renal biopsy was indicated
and the anatomopathological examination concluded to a FSGS involvement
(Figure 1 ). After ruling out the causes of secondary FSGS (human
immune-deficiency virus, hepatitis B virus, parvovirus B19, and
Cytomegalovirus infections, drug / toxic origin, adaptive FSGS by
nephronic reduction and glomerular hyperfiltration) we put the patient
on corticosteroid therapy (prednisone) at a dose of 1 mg/kg/day in
association with diuretics (furosemide and spironolactone) and an ACE
inhibitor (ramipril) for a period of 3 months, five albumin infusions
were also prescribed.

After three months of treatment, the edema as well as the nephrotic
syndrome have almost disappeared. Regarding his SpA, the patient is
currently awaiting a support agreement for Adalimumab from the social
insurance funds. He only receives analgesic treatment.

\textbf{Discussion:}

SpA is a chronic inflammatory rheumatism predominantly affecting young
men. Its prevalence is estimated between 0.3 and 2\% of the general
population (1). It can be responsible for axial, peripheral articular
and enthesitic involvement.

Renal involvement is rare in SpA, its frequency varies between 4.3 and
35\%(2). This impairment is often underestimated because of its late
onset (with an average of 6.6 to 19.4 years) (2) and the decrease in its
incidence mainly explained by the reduction in the use of NSAIDs after
the introduction of biotherapies in management of SpA (3).

The main circumstances of discovery of renal involvement during SpA are
edema, proteinuria, hematuria, increased blood pressure, urolithiasis,
deterioration of renal function and nephrotic syndrome (2,5,6).

Data from the literature report renal involvement in SpA to three main
etiologies represented by AA amyloidosis, IgA nephropathy and
urolithiasis. These different etiologies vary according to studies.
Ninety per cent of kidney damage are explained by amyloidosis (62\%) and
IgA nephropathy (30\%) (2,5--7). Literature data on other etiologies
(less than 8\%) are limited to case reports. Cases of extra-membranous
glomerulonephritis, mesangial glomerulonephritis with C3 and IgM
deposits, and membrano-proliferative glomerulonephritis have been
reported rarely (8--11). Rare cases of SpA-FSGS association have also
been reported, including 3 cases in 3 Tunisian series (2,6,12,13). To
the best of our knowledge, the present case is the fourth reported one
with no other identifiable cause of secondary FSGS.

Given the paucity of data in the literature, it seems difficult to
determine whether this association is etiological or a simple
coincidence. In our patient, before adopting an association between SpA
and FSGS, we excluded the causes of secondary FSGS (viral infections,
drug / toxic origin, adaptive FSGS by nephronic reduction and glomerular
hyperfiltration). Knowing that our patient had NSAIDs to control his SpA
activity, the presence of FSGS could be either due to previous
medication with NSAIDs or associated with his SpA\textbf{.}

A review of the literature showed that renal damage due to NSAIDs are
mainly acute interstitial nephritis (AIN), acute tubular injury (ATI),
minimal change disease (MCD), papillary necrosis (PN) and, rarely
membranous nephropathy (MN) (13,14). Literature data about the
relationship between NSAIDs and FSGS are controversial, an association
has been reported by some authors even in topical NSAIDs (15,16).
However Markowitz et al and Paueksakon et al in more recent study assert
that available data do not support a relationship between NSAIDs and
FSGS (14,17). Those data may support that FSGS in our patient can be
related to SpA. In summary, there is no study, as well as epidemiologic
evidence, that directly demonstrate the causal relationship between SpA
and FSGS. The role of NSAIDs, which are the main treatments for SpA, as
the cause of FSGS remains unclear. Since that, having eliminated the
other possible causes is in favor of SpA and FSGS association.

Our patient will be put on Adalinumab. This later has been used since
2006 for the treatment of SpA (18). It has also been used in refractory
cases of FSGS since 2014, it reduces proteinuria and protect kidney
function from degradation, it has also been reported as an alternative
in cases of resistance or allergy to rituximab in FSGS (19,20).

\textbf{Conclusion:}

We report a rare case of FSGS in a patient with SpA. Recognition of
renal impairment in SpA is important in order to guide necessary
nephroprotection measures and appropriate therapy before significant
renal damage occurs. The diagnosis should be made by renal biopsy which
in the majority of cases reveals amyloidosis or IgA nephropathy,
however, in rare cases, some rare associations can be discovered.

\par\null

\textbf{Author Agreement~}

I, Tbini Houssem, here by certify that all named authors have seen and
approved the final version of the manuscript being submitted. I on
behalf of all authors warrant that the article is the authors' original
work, hasn't received prior publication and isn't under consideration
for publication elsewhere. I confirm that the order of authors listed in
the manuscript has been approved by all of them.

Authors understand that the Corresponding Author is the sole contact for
the Editorial process. He is responsible for communicating with the
other authors about progress, submissions of revisions and final
approval of proofs.

\textbf{Conflict of Interest~Declaration:}

Authors declare having no conflict of interest.

\textbf{Funding}

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors.



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