Richard Johnson

Northern Illinois University · College of Law

Despite its discovery more than 150 years ago, the cause of primary hypertension remains unknown. Most studies suggest that hypertension involves genetic, congenital or acquired risk factors that result in a relative inability of the kidney to excrete salt (sodium chloride) in the kidneys. Here we review recent studies that suggest there may be two...

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks, but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be inv...

Planetary health embraces the concept that long-term human welfare depends on the well-being of its ecological systems. Current practices, however, have often ignored this concept and have led to an anthropocentric world, with the consequence of increased greenhouse gas emissions, heat stress, lack of clean water and pollution, that are threatening...

Heat shock protein 70 (HSP70) production is a stress-generated cellular response with high interspecies homology. HSP70 has both chaperone and cytokine functions and may induce, depending on the context, tolerogenic anti-inflammatory reactivity or immunogenic and autoimmune reactivity. Intracellular (chaperoning transit of antigens to MHC in antige...

Purpose of Review Oxygen is critical for the high output of energy (adenosine triphosphate) generated by oxidative phosphorylation in the mitochondria, and when oxygen delivery is impaired due to systemic hypoxia, impaired or reduced delivery of red blood cells, or from local ischemia, survival processes are activated. Recent Findings One major mec...

An important aspect of survival is to assure enough food, water, and oxygen. Here, we describe a recently discovered response that favors survival in times of scarcity, and it is initiated by either ingestion or production of fructose. Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated respo...

Gout is present in 25%, and hyperuricemia in 60% of patients with chronic kidney disease. Despite how common the association, the role of uric acid in the progression of kidney disease and in metabolic complications remains contested. Some authorities argue that the treatment of asymptomatic hyperuricemia in CKD is not indicated, and some have even...

Preeclampsia is a hypertensive disorder of pregnancy and is due to abnormal placentation. The pathogenesis remains unclear. Fructose is biologically distinct from glucose and has a critical role in fetal growth in early pregnancy. Many species, including humans, produce fructose in their placenta during the first trimester to assist fetal growth an...

Introduction: Activation of the focal adhesion kinase (FAK) in podocytes is involved in the pathogenesis of minimal change disease (MCD), but the pathway leading to its activation in this disease is unknown. Here, we tested whether podocyte β1 integrin is the upstream modulator of FAK activation and podocyte injury in experimental models of MCD-lik...

Steroid-sensitive nephrotic syndrome (SSNS) in childhood is usually due to minimal change disease (MCD). Unlike many glomerular conditions, SSNS/MCD is commonly precipitated by respiratory infections. Of interest, pulmonary inflammation release surfactants in circulation which are soluble agonists of SIRPα, a podocyte receptor that regulates integr...

Introduction: Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. Methods: We administered...

Improper hydration habits are commonly disregarded as a risk factor for the development of chronic diseases. Consuming an intake of water below recommendations (underhydration) in addition to the substitution of sugar-sweetened beverages (SSB) for water are habits deeply ingrained in several countries. This behavior is due to voluntary and involunt...

Background Exposure to environmental metals can cause nephrotoxicity. There is an international epidemic of chronic kidney disease of unknown cause (CKDu). Whether metal exposures contribute to kidney dysfunction in populations at risk for CKDu remains unresolved. Objective Urinary metals (arsenic, cadmium, nickel, and uranium) were examined in 22...

Objective We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D). Methods Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0....

Fructose metabolism and hyperuricemia have been shown to drive insulin resistance, metabolic syndrome, hepatic steatosis, hypertension, inflammation, and innate immune reactivity in experimental studies. We suggest that these adverse effects are at least in part the result of suppressed activity of sirtuins, particularly Sirtuin1. Deficiency of sir...

Primary aldosteronism is the most frequent cause of secondary hypertension. Here we present the hypothesis that the increasing incidence of primary aldosteronism is a consequence of chronic aldosterone stimulation from present day lifestyle and dietary conditions. We review epidemiological and pathophysiological evidence supporting the role of obes...

Fructose is a simple sugar that is the primary nutrient in fruits and honey, which are classically considered healthy foods. Fructose is also a major component of refined sugar, which has classically been viewed as a nonnutritional food or “empty calorie.” In the last decades the viewpoint that fructose is simply a caloric source of nutrition has s...

Introduction: Coronavirus 2019 (COVID-19) can increase catabolism and result in hyperuricemia. Uric acid (UA) potentially causes kidney damage by alteration of renal autoregulation, inhibition of endothelial cell proliferation, cell apoptosis, activation of the pro-inflammatory cascade, and crystal deposition. Hyperuricemia in patients with COVID-...

Introduction Minimal change disease (MCD) is considered a podocyte disorder triggered by unknown circulating factors. Here, we hypothesized that the endothelial cell is also involved in MCD. Methods We studied 45 children with idiopathic nephrotic syndrome (44 had steroid-sensitive nephrotic syndrome -SSNS-, and 12 had biopsy-proven MCD), 21 adult...

Hyperuricemia predicts the development of chronic kidney disease (CKD) and metabolic complications, but whether it has a causal role has been controversial. This is especially true given the 2 recently conducted randomized controlled trials that failed to show a benefit of lowering uric acid in type 1 diabetes-associated CKD and subjects with stage...

Provoked by sterile/nonsterile insults, prolonged monocyte mobilization and uncontrolled monocyte/macrophage activation can pose imminent or impending harm to the affected organs. Curiously, folate receptor beta (FRβ), with subnanomolar affinity for the vitamin folic acid (FA), is upregulated during immune activation in hematopoietic cells of the m...

Background. Recent studies suggest that fructose, as well as its metabolite, uric acid, have been associated with increased risk for both cancer incidence and growth. Both substances are known to cause oxidative stress to mitochondria and to reduce adenosine triphosphate (ATP) production by blocking aconitase in the Krebs cycle. The uricase mutatio...

Climate change should be of special concern for the nephrologist as the kidney has a critical role in protecting the host from dehydration, but is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, w...

Umami refers to the savoury taste that is mediated by monosodium glutamate (MSG) and enhanced by inosine monophosphate and other nucleotides. Umami foods have been suggested to increase the risk for obesity and metabolic syndrome but the mechanism is not understood. Here we show that MSG induces obesity, hypothalamic inflammation and central leptin...

Background Nephrotic syndrome is a common complication of pig-to-baboon kidney xenotransplantation (KXTx) that adversely affects outcomes. We have reported that upregulation of CD80 and down-regulation of SMPDL-3b in glomeruli have an important role in the development of proteinuria following pig-to-baboon KXTx. Recently we found induced expression...

Since activated macrophages express a functional folate receptor β (FRβ), targeting this macrophage population with folate-linked drugs could increase selectivity to treat inflammatory diseases. Using a macrophage-mediated anti-glomerular basement membrane (anti-GBM) glomerulonephritis (GN) in WKY rats, we investigated the effect of a novel folic a...

Background: Glomerular injury is a recognized complication of diabetic ketoacidosis (DKA), yet the tubular lesions are poorly understood. Objective: The aim of this prospective study was to evaluate the presence and reversibility of tubular injury during DKA in children with type 1 diabetes (T1D). Methods: Blood and urine samples were collecte...

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic...

Diabetic kidney disease (DKD) is a common complication of type 1 and 2 diabetes and often presents during adolescence and young adulthood. Given the growing incidence of both type 1 and type 2 diabetes in children and adolescents, DKD represents a significant public health problem. Acute kidney injury (AKI) in youth with diabetes is strongly associ...

Background: The consumption of sweetened beverages is associated with increased risk of metabolic syndrome, cardiovascular disease, and type 2 diabetes mellitus. Objective: We hypothesized that the metabolic effects of fructose in sugary beverages might be modulated by the speed of ingestion in addition to the overall amount. Design: Thirty he...

Classically, Non-Alcoholic Fatty Liver Disease (NAFLD) has been thought to be driven by excessive weight gain and obesity. The overall greater awareness of this disorder has led to its recognition in patients with normal body mass index (BMI). Ongoing research has helped to better understand potential causes of Lean NAFLD, the risks for more advanc...

In this narrative review, we present the hypothesis that key mutations in two genes, occurring 15 and 10 million years ago, were individually and then collectively adaptive for ancestral humans during periods of starvation, but are maladaptive in modern civilization (i.e., “thrifty genes”), with the consequence that these genes not only increase ou...

Chronic low-grade inflammation underlies the pathogenesis of non-communicable diseases, including chronic kidney diseases (CKD). Inflammation is a biologically active process accompanied with biochemical changes involving energy, amino acid, lipid and nucleotides. Recently, glycolysis has been observed to be increased in several inflammatory disord...

Introduction Agricultural workers laboring in thermally stressful environments are at increased risk for kidney injury and Chronic Kidney Disease of Unknown Origin (CKDu) and their environmental and occupational exposures have been considered to be important risk factors. This study examined the effects of repeated kidney stress from the simultaneo...

Increased serum uric acid (SUA) levels have been associated with various pathologic processes such as increased oxidative stress, inflammation, and endothelial dysfunction. Thus, it is not surprising that increased SUA is associated with various adverse outcomes including cardiovascular (CV) diseases. Recent epidemiological evidence suggests that i...

BACKGROUND Metabolic syndrome affects 35% of the adult population in developed countries associated with non-alcoholic steatohepatitis, insulin resistance, and cardiovascular events. Fatty infiltration of the pancreas, or pancreatic steatosis, is a risk factor for acute pancreatitis, pancreatic malignancies, and diabetes mellitus, yet its relations...

Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricem...

Excessive intake of fructose results in metabolic syndrome (MS) and kidney damage, partly mediated by its metabolism by fructokinase-C or ketohexokinase-C (KHK-C). Osthol has antioxidant properties, is capable of regulating adipogenesis, and inhibits KHK-C activity. Here, we examined the potential protective role of osthol in the development of kid...

Gout is present in one third of subjects with CKD but is usually an exclusion criterion in clinical trials investigating the role of uric acid in kidney disease. Bardin et al. report that one third of gouty subjects have hyperechoic medullas by ultrasound (consistent with crystalline deposits) that correlates with increased risk for hypertension an...

Currently, there is the paradox of low water intake but increased intake of sugar-sweetened beverages (SB) in several populations; those habits are associated with an increased prevalence of metabolic derangements and greater chronic disease mortality. Persistent heat dehydration and increased SB intake stimulate the continued release of vasopressi...

Figurines of women with obesity or who are pregnant (“Venus figurines”) from Upper Paleolithic Europe rank among the earliest art and endured from 38,000 to 14,000 BP (before present), one of the most arduous climatic periods in human history. We propose that the Venus representation relates to human adaptation to climate change. During this period...

Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal...

Experimental studies suggest involvement of trimethylamine N-oxide (TMAO) in the aetiology of cardiometabolic diseases and chronic kidney disease (CKD), in part via metabolism of ingested food. Using a comparative biomimetic approach, we have investigated circulating levels of the gut metabolites betaine, choline, and TMAO in human CKD, across anim...

Background: The causal relationship between gout and renal transplant outcomes is difficult to assess due to multiple interacting covariates. This study sought to estimate the independent effect of new-onset gout on renal transplant outcomes using a methodology that accounted for these interactions. Methods: This study analyzed data on patients...

Kidney disease, especially when it is associated with a reduction in estimated glomerular filtration rate, can be associated with an increase in serum urate (uric acid), suggesting that hyperuricemia in subjects with kidney disease may be a strictly secondary phenomenon. Mendelian randomization studies that evaluate genetic scores regulating serum...

Gout, an inflammatory arthritis, affects over nine million people in the US with increasing prevalence. Some medical societies do not recommend treating gout unless it is recurrent. While soft tissue urate deposits (tophi), resultant bone erosions, and joint inflammation are frequently recognized in gout, urate crystal deposits in other sites have...

Several behavioral disorders, including attention deficit hyperactivity disorder (ADHD), bipolar disorder, and aggressive behaviors are linked with sugar intake and obesity. The reason(s) for this association has been unclear. Here we present a hypothesis supporting a role for fructose, a component of sugar and high fructose corn syrup (HFCS), and...

The loss of cognitive function in Alzheimer’s disease is pathologically linked with neurofibrillary tangles, amyloid deposition, and loss of neuronal communication. Cerebral insulin resistance and mitochondrial dysfunction have emerged as important contributors to pathogenesis supporting our hypothesis that cerebral fructose metabolism is a key ini...

Background: Sugarcane workers in Central America experience a heavy burden of chronic kidney disease of unknown origin. We conducted a pilot study among worker proxies in Guatemala to characterize exposures to particulate matter, silica, heavy metals, and glyphosate, as well as to examine potential nephrotoxic exposures. Methods: Air, soil, and...

The objective of this study was to compare the ratio of renal oxygen availability (RO2) to GFR (RO2:GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygenation level depen...

Abstract Obesity and metabolic syndrome are strongly associated with cancer, and these disorders may share a common mechanism. Recently, fructose has emerged as a driving force to develop obesity and metabolic syndrome. Thus, we assume that fructose may be the mechanism to explain why obesity and metabolic syndrome are linked with cancer. Clinical...

Background Chronic kidney disease of unknown origin (CKDu) is an epidemic that disproportionately affects young agriculture workers in hot regions. It has been hypothesized that repeated acute kidney injury may play a role in the development of disease. Methods Latent class mixed models were used to identify groups of Guatemalan sugarcane harveste...

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes...

Intake of sugars and especially the fructose component, is strongly associated with the development of obesity and metabolic syndrome, but the relative role of taste versus metabolism in driving preference, intake and metabolic outcome is not fully understood. To this end, we aimed to evaluate the preference for sweet substances and the tendency to...

Background: Chronic kidney disease of non-traditional origin (CKDnt) is common among Mesoamerican sugarcane workers. Recurrent heat stress and dehydration is a leading hypothesis. Evidence indicate a key role of inflammation. Methods: Starting in sports and heat pathophysiology literature, we develop a theoretical framework of how strenuous work...

Intake of fructose-containing sugars is strongly associated with metabolic syndrome. Compared with other sugars, dietary fructose is uniquely metabolized by fructokinase. However, the tissue-specific role of fructokinase in sugar-induced metabolic syndrome, and the specific roles of glucose and fructose in driving it, is not fully understood. Here,...

Background: We aimed to determine the prevalence of decreased kidney function in a potential chronic kidney disease (KD) of unknown aetiology hotspot in Mexico, assess its distribution across occupations and examine the associated risk factors. Methods: A cross-sectional study collected sociodemographic, occupational, medical and biometric data...

The potential contribution of serum osmolarity in the modulation of blood pressure has not been evaluated. This study was done to examine the relationship between hyperosmolarity and hypertension in a five-year longitudinal design. We enrolled 10,157 normotensive subjects without diabetes who developed hypertension subsequently as determined by ann...

Background: Urinary CD80 has emerged as potential biomarker in idiopathic nephrotic syndrome (INS). However, its cellular source remains controversial. The aim of the study was to assess whether CD80 is truly expressed by glomerular cells in INS patients during relapse and in the LPS mouse model of podocyte injury. Methods: The presence of CD80...

We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/gluc...

Understanding fructose metabolism might provide insights to renal pathophysiology. To support systemic glucose concentration, the proximal tubular cells reabsorb fructose as a substrate for gluconeogenesis. However, in instances when fructose intake is excessive, fructose metabolism is costly, resulting in energy depletion, uric acid generation, in...

Background: Vasopressin is elevated in response to heat and dehydration and has been postulated to have a role in the chronic kidney disease of unknown origin being observed in Central America. The aims of this study were to examine whether the vasopressin pathway, as measured by copeptin, is associated with the presence of kidney dysfunction, and...

The optimal range of serum uric acid (urate) associated with the lowest risk for developing cardiometabolic diseases is unknown in a generally healthy population. This 5-year cohort study is designed to identify the optimal range of serum urate. The data were collected from 13,070 Japanese between ages 30 and 85 at the baseline (2004) from the Cent...